Comparing the efficacy of low-load resistance exercise combined with blood flow restriction versus conventional-load resistance exercise in Chinese community-dwelling older people with sarcopenic obesity: a study protocol for a randomised controlled trial.

INTRODUCTION: Sarcopenic obesity (SO) is characterised by decreased muscle mass, diminished muscle strength and/or reduced physical performance and a high percentage of body fat (PBF). Conventional-load resistance exercise (CRE) may be difficult for older people with SO owing to their declining physical functions. Low-load resistance exercise (LRE) combined with blood flow restriction (BFR; LRE-BFR) is a viable alternative to CRE for improving muscle mass and strength and potential exercise mode for managing SO. This study has two objectives: (1) to comprehensively evaluate the efficacy of CRE and LRE-BFR in improving body composition, muscle strength, physical performance, haematological parameters, cardiovascular disease (CVD) risk factors and quality of life and (2) to compare the efficacy of CRE and LRE-BFR and explore their potential mechanisms. METHODS AND ANALYSIS: This work is a 12-week assessor-blinded randomised clinical trial that will be conducted thrice a week. Sarcopenia will be defined using the Asian Working Group for Sarcopenia 2019, and obesity will be determined using the criteria developed by the World Health Organization. Community-dwelling older people aged ≥ 65 years will be screened as the participants using inclusion and exclusion criteria. A total of 33 participants will be randomised into a CRE group (n = 11), an LRE-BFR group (n = 11) and a control group that will be given only health education (n = 11). The primary outcomes will be knee extensor strength and PBF, and the secondary outcomes will be body composition, anthropometric measurements, muscle strength of upper limbs, physical performance, haematological parameters, CVD risk factors and quality of life. The outcomes will be measured at the baseline (week 0), end of the intervention (week 12) and follow up (week 24). All the collected data will be analysed following the intention-to-treat principle. ETHICS AND DISSEMINATION: The Ethics Research Committee has approved this study (approval No. CMEC-2022-KT-51). Changes or developments in this study will be reported at www.chictr.org.cn . TRIAL REGISTRATION: ChiCTR2300067296 (3 January 2023).

11-Ethoxyviburtinal improves chronic restraint stress-induced anxiety-like behaviors in gender-specific mice via PI3K/Akt and E2 /ERß signaling pathways.

Anxiety disorder is a chronic and disabling psychiatric disorder that is more prevalent in females than in males. 11-Ethoxyviburtinal is an iridoid extracted from Valeriana jatamansi Jones, which has anxiolytic potential. The aim of the present work was to study the anxiolytic efficacy and mechanism of 11-ethoxyviburtinal in gender-specific mice. We first evaluated the anxiolytic-like efficacy of 11-ethoxyviburtinal in chronic restraint stress (CRS) mice of different sexes through behavioral experiments and biochemical indexes. In addition, network pharmacology and molecular docking were used to predict potential targets and important pathways for the treatment of anxiety disorder with 11-ethoxyviburtinal. Finally, the influence of 11-ethoxyviburtinal on phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, estrogen receptor ß (ERß) expression, and anxiety-like behavior in mice was verified by western blotting, immunohistochemistry staining, antagonist intervention methods, and behavioral experiments. 11-ethoxyviburtinal alleviated the anxiety-like behaviors induced by CRS and inhibited neurotransmitter dysregulation and HPA axis hyperactivity. It inhibited the abnormal activation of the PI3K/Akt signaling pathway, modulated estrogen production, and promoted ERß expression in mice. In addition, the female mice may be more sensitive to the pharmacological effects of 11-ethoxyviburtinal. 11-ethoxyviburtinal may exert its anxiolytic-like effects through PI3K/Akt and E2/ERß signaling pathways. Meanwhile, by comparing the male and female mice, gender differences may affect the therapy and development of anxiety disorder.

Scutellarin Alleviates Ischemic Brain Injury in the Acute Phase by Affecting the Activity of Neurotransmitters in Neurons.

Cerebral ischemic stroke is a common neuron loss disease that is caused by the interruption of the blood supply to the brain. In order to enhance the CIS outcome, both identifying the treatment target of ischemic brain damage in the acute phase and developing effective therapies are urgently needed. Scutellarin had been found to be beneficial to ischemic injuries and has been shown to have potent effects in clinical application on both stroke and myocardial infarction. However, whether scutellarin improves ischemic brain damage in the acute phase remains unknown. In this study, the protective effects of scutellarin on ischemic brain damage in the acute phase (within 12 h) were illustrated. In middle cerebral artery occlusion and reperfusion (MCAO/R) modeling rats, the Z-Longa score was significantly down-regulated by 25% and 23.1%, and the brain infarct size was reduced by 26.95 ± 0.03% and 25.63 ± 0.02% when responding to high-dose and low-dose scutellarin treatments, respectively. H&E and TUNEL staining results indicated that the neuron loss of the ischemic region was improved under scutellarin treatment. In order to investigate the mechanism of scutellarin's effects on ischemic brain damage in the acute phase, changes in proteins and metabolites were analyzed. The suppression of scutellarin on the glutamate-inducing excitatory amino acid toxicity was strongly indicated in the study of both proteomics and metabolomics. A molecular docking experiment presented strong interactions between scutellarin and glutamate receptors, which score much higher than those of memantine. Further, by performing a parallel reaction monitoring-mass spectrometry (PRM-MS) study on both the cortex and hippocampus tissue of the ischemic region, we screened the scutellarin-regulating molecules that are involved in both the release and transportation of neurotransmitters. It was found that the aberrant levels of glutamate receptors, including EAAT2, GRIN1, GRIN2B, and GRM1, as well as of other glutamatergic pathway-involving proteins, including CAMKK2, PSD95, and nNOS, were significantly regulated in the ischemic cortex. In the hippocampus, EAAT2, GRIN1, nNOS, and CAM were significantly regulated. Taken together, scutellarin exerts potent effects on ischemic brain damage in the acute phase by regulating the activity of neurotransmitters and reducing the toxicity of excitatory amino acids in in neurons.

Nardostachys jatamansi and levodopa combination alleviates Parkinson's disease symptoms in rats through activation of Nrf2 and inhibition of NLRP3 signaling pathways.

CONTEXT: Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD. OBJECTIVE: To explore the synergistic effect of NJ combined with levodopa against PD. MATERIALS AND METHODS: The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways. RESULTS: Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23, p < 0.01), enhanced the stay time on the rotating rod (84.86 ± 18.15 vs. 71.36 ± 17.53, p < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway. DISCUSSION AND CONCLUSIONS: NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.

Nootkatone alleviates rotenone-induced Parkinson's disease symptoms through activation of the PI3K/Akt signaling pathway.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Nootkatone (NKT) has been shown to have neuroprotective, anti-inflammatory, and antioxidant effects and in this study, we systematically studied the efficacy and mechanism of action of NKT in rotenone (ROT)-induced PD rats. Firstly, through behavioral experiments and brain tissue staining, we found that NKT alleviated behavioral dysfunction and protected dopaminergic neurons associated with ROT-induced PD rats. Next, target prediction, protein-protein interaction (PPI), Gene Ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of NKT for the potential treatment of PD. Furthermore, we also applied molecular docking to predict the binding capacity of NKT and related targets. Additionally, in vivo experiments confirmed that NKT could inhibit the expression of Mitogen-activated protein kinase 3 (MAPK3) by activating the PI3K/Akt signaling pathway, reducing neuroinflammation, and ultimately ameliorating ROT-induced PD symptoms. Taken together, the results of the study provide a clear explanation for the remission of PD symptoms by NKT, suggesting that it may be a promising candidate for the treatment of PD.

[Effects of Nardostachys jatamansi on gut microbiota of rats with Parkinson's disease].

Under the guidance of the traditional Chinese medicine(TCM) theory of "Zangfu-organs of spleen and stomach" and the modern theory of "microbiota-gut-brain axis", this study explored the effects of Nardostachys jatamansi on the gut microbiota of rats with Parkinson's disease(PD). The 40 SD rats were randomly divided into the control group, PD model group, levodopa group, and Nardostachys jatamansi ethanol extract group. The PD model was established by subcutaneous injection of rotenone in the neck and back area. After 14 days of intragastric administration, the PD rats' behaviors were analyzed through open field test, inclined plane test, and pole test. After the behavioral tests, the striatum, colon, and colon contents of rats in each group were collected. Western blot was employed to detect the protein expression of tyrosine hydroxylase(TH) and α-synuclein(α-syn) in striatum and that of α-syn in colon. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and nuclear factor-kappa B(NF-κB) in striatum and colon. High-throughput sequencing of 16 S rRNA gene was conducted to detect the differences in microbial diversity, abundance, differential phyla, and dominant bacteria of rats between groups. The results indicated that Nar. ethanol extract could relieve dyskinesia, reverse the increased levels of α-syn, TNF-α, IL-1ß, and NF-κB in striatum, and improve the protein expression of TH in striatum of PD rats. The α diversity analysis indicated a significant decrease in diversity and abundance of gut microbiota in the PD model. The results of linear discriminant analysis effect size(LEfSe) of dominant bacteria indicated that Nardostachys jatamansi ethanol extract increased the relative abundance of Clotridiaceae, Lachnospiraceae, and Anaerostipes, and reversed the increased relative abundance of Proteobacteria, Gammaproteobacteria, Enterobacteriaceae, and Escherichia-Shigella in PD model group to exhibit the neuroprotective effect. In summary, the results indicated that Nar. ethanol extract exert the therapeutic effect on PD rats. Specifically, the extract may regulate gut microbiota, decrease the levels of proinflammatory cytokines, and reduce the protein aggregation of α-syn in the colon and striatum to alleviate intestinal inflammation and neuroinflammation. This study provides a basis for combining the theory of "Zangfu-organs of spleen and stomach" with the theory of "microbiota-gut-brain axis" to treat PD.

[Study on mechanism of Valerianae Jatamansi Rhizoma et Radix against post-traumatic stress disorder based on molecular docking and network pharmacology].

This paper aims to investigate the active components and mechanism of Valerianae Jatamansi Rhizoma et Radix against post-traumatic stress disorder(PTSD) based on network pharmacology and molecular docking. The main components and targets of Valerianae Jatamansi Rhizoma et Radix were obtained by literature mining methods, SwissTargetPrediction, BATMAN and ETCM database. PTSD-related genes were collected from DrugBank, TTD and CTD databases. The protein-protein interaction(PPI) network was constructed based on STRING, and the core targets of Valerianae Jatamansi Rhizoma et Radix in the treatment of PTSD were selected according to the topological parameters. Cytoscape 3.7.2 was used to construct the compound-target network. DAVID database was used for GO enrichment analysis and KEGG enrichment analysis. The relationship network of "compound-target-pathway" was constructed through Cytoscape 3.7.2 to analyze and obtain the key targets and their corresponding components in the network, and their results were verified by molecular docking. The results showed that a total of 47 components(such as valeraldehyde, dihydrovalerin, valerate, chlorovaltrate K, 8-hydroxypinoresinol, 6-hydroxyluteolin, apigenin, farnesin, vanillin, luteolin, kaempferol, glycosmisic acid and pogostemon) of Valerianae Jatamansi Rhizoma et Radix may act on 94 key targets such as CNR1, MAOA, NR3 C1, MAPK14, MAPK8, HTR2 C and DRD2. Totally 29 GO terms were obtained by GO functional enrichment analysis(P<0.05), and 20 signaling pathways were obtained from KEGG pathway enrichment, mainly involving neuroactive ligand-receptor interaction, serotonergic synapse, calcium signaling pathway, cAMP signaling pathway, dopaminergic synapse, retrograde endocannabinoid signaling, neurotrophin signaling pathway, gap junction, cholinergic synapse, estrogen signaling pathway, glutamatergic synapse and long-term potentiation. Molecular docking analysis showed that hydrogen bonding, π-π interaction and hydrophobic effecting may be the main forms of interaction. This study used the network of compound-target-pathway and molecular docking technology to screen the effective components of Valerianae Jatamansi Rhizoma et Radix against PTSD, and explore its anti-PTSD mechanism, so as to provide scientific basis for exploring the anti-PTSD drugs from traditional Chinese medicine and clarifying its mechanism of action.

[Spectrum-effect relationship of the blood-activating efficacy of Notoginseng Radix et Rhizoma].

This study aims to establish the high-performance liquid chromatography(HPLC) fingerprints of different batches of Notoginseng Radix et Rhizoma, determine their pharmacodynamic indexes of promoting blood circulation, and explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the efficacy of promoting blood circulation. Firstly, the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma were established. Then, the pharmacodynamic indexes were determined after the capillary coagulation experiment and the cerebral ischemia-reperfusion in rats, including capillary coagulation time, percentage of cerebral ischemic area, cerebral water loss rate, and brain-body index. Afterward, the partial least-squares method was used to explore the spectrum-effect relationship between the chemical components of Notoginseng Radix et Rhizoma and the pharmacodynamic indexes. The results showed that this study successfully established the HPLC fingerprints of different batches of Notoginseng Radix et Rhizoma, found 23 common peaks, and identified 12 of them, all of which were saponins. The method was proved stable and reliable. Both the capillary coagulation experiment and the middle cerebral artery occlusion(MCAO)-induced cerebral ischemia-reperfusion experiment on rats revealed that there were obvious differences in the pharmacodynamic indexes of different batches of Notoginseng Radix et Rhizoma. The relationships between 23 common components of Notoginseng Radix et Rhizoma in different batches and the pharmacodynamic indexes were discussed by means of spectrum-effect correlation analysis, of which 17 components had positive effects while 6 components had negative effects on the pharmacodynamic indexes. This study provides a certain reference basis for the clinical rational use and quality control of Notoginseng Radix et Rhizoma.

[Spectrum-effect relationship of hemostatic effects of Notoginseng Radix et Rhizoma with different commodity specifications].

This article aims to establish the fingerprints, determine the hemostatic pharmacodynamic indicators, and explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in 12 different specifications. Firstly, HPLC and liquid chromatography-mass spectrometry(LC-MS) were employed to establish the fingerprints of Notoginseng Radix et Rhizoma. The rat plasma recalcification experiment and the rat gastric bleeding experiment were conducted to determine the pharmacodynamic indicators, including plasma recalcification time(PRT), thrombin time(TT), prothrombin time(PT), and activated partial thromboplastin time(APTT). Afterwards, the partial least squares method was employed to explore the spectrum-effect relationship of Notoginseng Radix et Rhizoma in different specifications. Twenty-six common peaks were detected in the HPLC fingerprints of different specifications of Notoginseng Radix et Rhizoma, and 11 out of the 26 common peaks represented saponins. The content of dencichine was determined by LC-MS. The rat experiments showed that the pharmacodynamic indicators were significantly different among different specifications of Notoginseng Radix et Rhizoma. The spectrum-effect relationship was explored between 27 common components and pharmacodynamic indicators. Among them, 16 components had positive effects on the pharmacodynamic indicators of Notoginseng Radix et Rhizoma, and 11 exerted negative effects. This study provides a basis for the precision medication and quality control of Notoginseng Radix et Rhizoma.

Identification of Bioactive Chemical Markers in Zhi zhu xiang Improving Anxiety in Rat by Fingerprint-Efficacy Study.

Zhi zhu xiang (ZZX for short) is the root and rhizome of Valeriana jatamansi Jones, which is a Traditional Chinese Medicine (TCM) used to treat various mood disorders for more than 2000 years, especially anxiety. The aim of the present work was to identify the bioactive chemical markers in Zhi zhu xiang improving anxiety in rats by a fingerprint-efficacy study. More specifically, the chemical fingerprint of ZZX samples collected from 10 different regions was determined by High Performance Liquid Chromatography (HPLC) and the similarity analyses were calculated based on 10 common characteristic peaks. The anti-anxiety effect of ZZX on empty bottle stimulated rats was examined through the Open Field Test (OFT) and the Elevated Plus Maze Test (EPM). Then we measured the concentration of CRF, ACTH, and CORT in rat's plasma by the enzyme-linked immune sorbent assay (ELISA) kit, while the concentration of monoamine and metabolites (NE, DA, DOPAC, HVA, 5-HT, 5-HIAA) in the rat's cerebral cortex and hippocampus was analysed by HPLC coupled with an Electrochemical Detector. At last, the fingerprint-efficacy study between chemical fingerprint and anti-anxiety effect of ZZX was accomplished by partial least squares regression (PLSR). As a result, we screened out four compounds (hesperidin, isochlorogenic acid A, isochlorogenic acid B and isochlorogenic acid C) as the bioactive chemical markers for the anti-anxiety effect of ZZX. The fingerprint-efficacy study we established might provide a feasible way and some elicitation for the identification of the bioactive chemical markers for TCM.

Flexible and powerful strategy for qualitative and quantitative analysis of valepotriates in Valeriana jatamansi Jones using high-performance liquid chromatography with linear ion trap Orbitrap mass spectrometry.

Valeriana jatamansi Jones is an important medicinal plant and its quality is closely related to its region of origin. In the current study, we utilized a flexible and powerful strategy for comprehensive evaluation of the quality diversity for 15 regions in China. The method was based on a hybrid linear ion trap-Orbitrap mass spectrometry platform. For structure characterization, fragmentation patterns were detected by analyzing a series of standard compounds using data dependent multistage mass spectrometry acquisition. A fragment ion database for valepotriates was established, and the acquired data were high throughput filtered by fragment ion search for compound identification. For quantitative purposes, we normalized the mass spectrometry data of 15 samples using SIEVE 2.0 and the differences in composition were analyzed using principal component analysis combined with hierarchical clustering analysis. The results identified a total of 92 compounds from Valeriana jatamansi Jones. Samples from Dali, Kunming, and Baoshan have better qualities and concentrations of the main active constituents. To verify our strategy, we compared the valtrate, acevaltrate, and baldrinal contents using high-performance liquid chromatography with diode array detector. We developed and validated a comprehensive qualitative and quantitative analytical method to achieve quality control of Valeriana jatamansi Jones.

Anti-Anxiety Effect of (-)-Syringaresnol-4-O-ß-d-apiofuranosyl-(1→2)-ß-d-glucopyranoside from Albizzia julibrissin Durazz (Leguminosae).

Albizzia julibrissin Durazz, a Chinese Medicine, is commonly used for its anti-anxiety effects. (-)-syringaresnol-4-O-ß-d-apiofuranosyl-(1→2)-ß-d-glucopyranoside (SAG) is the main ingredient of Albizzia julibrissin Durazz. The present study investigated the anxiolytic effect and potential mechanisms on the HPA axis and monoaminergic systems of SAG on acute restraint-stressed rats. The anxiolytic effect of SAG was examined through an open field test and an elevated plus maze test. The concentration of CRF, ACTH, and CORT in plasma was examined by an enzyme-linked immune sorbent assay (ELISA) kit while neurotransmitters in the cerebral cortex and hippocampus of the brain were examined by High Performance Liquid Chromatography (HPLC). We show that repeated treatment with SAG (3.6 mg/kg, p.o.) significantly increased the number and time spent on the central entries in the open-field test when compared to the vehicle/stressed group. In the elevated plus maze test, 3.6 mg/kg SAG could increase the percentage of entries into and time spent on the open arms of the elevated plus maze. In addition, the concentration of CRF, ACTH, and CORT in plasma and neurotransmitters (NE, 5-HT, DA and their metabolites 5-HIAA, DOPAC, and HVA) in the cerebral cortex and hippocampus of the brain were decreased after SAG treatment, as compared to the repeated acute restraint-stressed rats. These results suggest that SAG is a potential anti-anxiety drug candidate.

[Clinical study on compound prescription with Valerianae Jatamansi Rhizoma et Radix in treatment of generalized anxiety disorder].

This study was aimed to observe the clinical efficacy of anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix (ACPV) in treating liver Qi stagnation and feel ill at ease type generalized anxiety disorder (GAD). Sixty-seven patients diagnosed as GAD with stagnation of liver Qi and feel ill at ease were randomly divided into treatment group and control group. Patients in treatment group (n=34) was treated with ACPV decoction, and patients in control group (n=33) were treated with deanxit. Both groups were treated with respective drugs for 4 weeks. HAMA scale, traditional Chinese medicine (TCM) symptom scale (liver Qi stagnation and feel ill at ease type) and salivary cortisol levels were measured before and 2 weeks and 4 weeks after drug treatment. The life events scale (LES) and drug safety evaluation were performed before and after 4 weeks treatment. Two patients were excluded according to LES, and 5 patients were discontinued. Sixty patients were enrolled in the study finally (30 cases in each group). As compared with baseline, HAMA scores in both groups were significantly decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). After 2 weeks and 4 weeks treatment, the TCM syndrome score in both group was also significantly improved (P<0.01). Moreover, the salivary cortisol levels in both groups were also decreased at 2 weeks and 4 weeks (P<0.05, P<0.01). The total efficiency between two groups had no statistically significant difference after 2 weeks treatment and 4 weeks treatment; moreover, no statistically significant differences were observed between two groups in HAMA scores, TCM syndrome scale scores and salivary cortisol levels between two groups. The incidence of adverse reactions in the treatment group was significantly lower than that in the control group (P<0.01), and there were no obvious side effects in general physical examination during the period of treatment. Thus, anxiolytic compound prescription with Valerianae Jatamansi Rhizoma et Radix is effective for GAD (stagnation of liver Qi and feel ill at ease type).

[Advanced in studies on anxiolytic effects of natural flavonoids].

Anxiety is one of the most common diseases endangering human health. Its pathogenesis is complex, the studies on the mechanisms of anxiety disorder are concentrated on neurotransmitter, neuroendocrine, immunologic system. Flavonoids are a kind of compounds which possess a variety of physiological activity, used in plenty of diseases. In recent years, researches of natural flavonoids on anti-anxiety were increasing, but contents were incomplete. It was just involved several neurotransmitters in research area. This paper is based on different anxiolytic effect mechanisms and structure-activity relationships of natural flavonoids, summarizing the researches of domestic and foreign, which can serve as a reference for further studies on anxiolytic effects of natural flavonoids.

The effects of Nardosinone on levodopa intervention in the treatment of Parkinson's disease.

BACKGROUND: The roots and rhizomes of Nardostachys jatamansi DC. are reported to be useful for the treatment of Parkinson's disease (PD). Previous research has also shown that Nardosinone, the main active component isolated from Nardostachys jatamansi DC., exhibits the potential to treat PD. AIM OF THE STUDY: To investigate how the effects of Nardosinone could assist levodopa in the treatment of PD, how this process changes the intestinal flora, and to explore the effective forms of Nardosinone in the intestinal flora. MATERIAL AND METHODS: We used behavioral experiments, and hematoxylin-eosin staining and immunohistochemical staining, to investigate the effects of a combination of Nardosinone and levodopa on rotenone-induced PD rats. In addition, we used LC/MS-MS to determine the levels of levodopa, 5-hydroxytryptamine, dopamine and its metabolite 3, 4-dihydroxyphenylacetic acid, and homovanillic acid, to investigate the effect of the intestinal flora on co-administration in the treatment of PD. LC/MS-MS was also used to detect the metabolites of Nardosinone on the gastrointestinal tract and intestinal flora. RESULTS: The behavioral disorders and neuronal damage associated with PD were significantly improved following the co-administration. Analysis also revealed that the co-administration increased the levels of five neurotransmitters in the striatum, plasma and feces. In vitro experiments further demonstrated that the levels of dopamine and levodopa were increased in the intestinal flora. In total, five metabolites of Nardosinone were identified. CONCLUSION: Our findings indicate that Nardosinone and its metabolites might act as a potential adjutant to enhance the efficacy of levodopa via the intestinal flora, thus expanding the therapeutic potential of the combination of Chinese and Western medicine as a treatment method for PD.

Screening and verification of hemostatic effective components group of Panax Notoginseng based on spectrum-effect relationships.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax Notoginseng (PN) can disperse blood stasis, hemostasis, and detumescence analgesic, which can be used for hemoptysis, hematemesis and another traumatic bleeding, and it is known as "A miracle hemostatic medicine". Studies show that the chemical composition of PN is relatively comprehensive, however, its hemostatic active ingredients have not been fully clarified. AIM OF STUDY: This study aimed to clarify the hemostatic effective components group (HECG) of PN, provide a foundation for the assessment of PN's quality and its comprehensive development, and for further studies on the pharmacodynamic material basis of other Traditional Chinese Medicines (TCMs). MATERIALS AND METHODS: UPLC-MS was used to establish the fingerprint and identify the common peaks in 44 batches of PN extracts (PNE). In addition, the plasma recalcification time and in vitro coagulation time were measured. For spectrum-effect analysis, bivariate correlation analysis (BCA) and partial least squares regression analysis (PLSR) were used to screen the hemostasis candidate active monomers of PN. The monomers were prepared by combining several preparative chromatography techniques. The efficacy was verified by plasma recalcification time, in vitro coagulation time, and a rat model of gastric hemorrhage. RESULTS: A total of 30 common peaks and hemostatic efficacy indexes of 44 batches of PNE were obtained. A total of 18 components were positively correlated with the comprehensive coagulation index by two statistical methods. Six and eleven monomers were obtained respectively by chromatographic preparation and procurement, and one monomer was eliminated due to preparation difficulty and other reasons. Seven active monomers with direct hemostatic effect and one active monomer with synergistic hemostatic effect were screened through plasma recalcification time, and their combinations were used as candidate HECG for hemostatic effect verification. The results of in vitro experiments showed that plasma recalcification time and in vitro coagulation time were significantly reduced (P < 0.05) in the HECG group, compared to the PNE group. The results of in vivo experiment also indicated that the hemostatic effect of HECG was comparable to that of PNE and PN powder. CONCLUSION: The composition and efficacy of the HECG of PN were screened and verified using the spectral correlation method and in vivo and in vitro efficacy verification; the HECG included Dencichine, Ginsenoside Rg1, Ginsenoside Rd, Ginsenoside Rh1, Ginsenoside F1, Notoginsenoside R1, Notoginsenoside Ft1 and Notoginsenoside Fe. These results laid a foundation for the quality evaluation of PN and provided a reference for the basic research of pharmacodynamic material basis of other TCMs.

[Nardosinone reduces neuronal injury induced by oxygen-glucose deprivation in primary cortical cultures].

The aim of the study is to investigate the effect of nardosinone (Nar) on neuronal injury induced by oxygen-glucose deprivation (OGD) in primary cortical cultures isolated from embryos at gestational day 14. MTT method was used to determine the dosage regimen of Nar in primary neuronal cultures and observe the influence of Nar on the neurons suffering OGD; Western blotting analysis was used to detect expressions of protein kinase A (PKA), Ras related protein 1 (Rap1), mitogen-activated protein kinase kinase 1 (MEK1) and phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2) of OGD-injured or uninjured primary cultured neurons after Nar treatment. Results showed that Nar (50 and 100 micromol x L(-1)) improved the cell viability during OGD damage (P < 0.01) and increased the expression of PKA, Rap1, MEK1 and p-ERK1/2 in injured neurons. Additionally, elevations of PKA, Rapl, MEK1 and p-ERK1/2 in uninjured neurons were caused by Nar (50, 100 and 200 micromol x L(-1)) with a dose-dependent tenclency as well (P < 0.01). In conclusion, Nar could protect against the neuronal injury exposed to OGD, which may be relevant to the promotion of PKA and ERK signaling pathway.

[Mass spectrum characterization of five valepotriates by electrospray ionization tandem mass spectrometry].

OBJECTIVE: To discuss mass spectrum characterization of five valepotriates including 'monoene' type (didrovaltrate), 'diene' type (valtrate, acevaltrate) and 'four-olefinic' type (baldrinal and homobaldrinal) by electrospray ionization tandem mass spectrometry (ESI-MS(n)). METHOD: This study was carried out on the basis of electrospray ionization tandem mass spectrometric method and analysis of multistage fragments. RESULT: The fragmentation patterns and structural assignment of 'monoene' type, 'diene' type and 'four-olefinic' type valepotriates in ESI-MSn under positive mode were summarized. CONCLUSION: The compounds have a strong pyrolysis rules and it can provide reference date for valepotriates in rapid structural identification, quantitative analysis and pharmacokinetic study.

Anxiolytic-like effect of Suanzaoren-Wuweizi herb-pair and evidence for the involvement of the monoaminergic system in mice based on network pharmacology.

BACKGROUND: Suanzaoren-Wuweizi herb-pair (SWHP), composed of Zizyphi Spinosi Semen (Suanzaoren in Chinese) and Schisandrae Chinensis Fructus (Wuweizi in Chinese), is a traditional herbal formula that has been extensively used for the treatment of insomnia. The study aimed to explore the targets and signal pathways of Suanzaoren-Wuweizi (S-W) in the treatment of anxiety by network pharmacology, and to verify the pharmacodynamics and key targets of SWHP in mice. METHODS: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) as well as literature mining were used to obtain the main chemical ingredients of Suanzaoren and Wuweizi. The SwissTargetPrediction platform was used to predict drug-related targets. The GeneCards, TTD, DisGeNET and OMIM databases were used to obtain potential targets for the treatment of anxiety with the chemical components of S-W. Drug-disease intersection genes were selected, and a protein-protein interaction (PPI) network was constructed using STRING. The core targets of S-W in the treatment of anxiety were selected according to the topological parameters, and GO functional enrichment as well as KEGG pathways enrichment analyses were performed for potential targets. The relationship network of the "drug-active ingredient-disease-target-pathway" was constructed through Cytoscape 3.8.0. The pharmacodynamics of SWHP in the treatment of anxiety was evaluated by the elevated plus maze (EPM), the light/dark box test (LDB) and the open field test (OFT). The mechanisms were examined by measuring monoamine neurotransmitters in brain of mice. RESULTS: The results showed that there were 13 active ingredients for the treatment of anxiety in the network. This includes sanjoinenine, swertisin, daucosterol, schizandrer B, wuweizisu C and gomisin-A. Additionally, there were 148 targets, such as AKT1, TNF, SLC6A4, SLC6A3, EGFR, ESR1, HSP90AA1, CCND1, and DRD2, mainly involved in neuroactive ligand-receptor interactions, the Serotonergic synapse pathway and the cAMP signaling pathway. After 1 week of treatment, SWHP (2 and 3 g/kg) induced a significant increase on the percentage of entries into and time spent on the open arms of the EPM. In the LDB test, SWHP exerted anxiolytic-like effect at 2 g/kg. In the open-field test, SWHP (2 g/kg) increased the number of central entries and time spent in central areas. The levels of brain monoamines (5-HT and DA) and their metabolites (5-HIAA, DOPAC) were decreased after SWHP treatment. CONCLUSIONS: The anti-anxiety effect of SWHP may be mediated by regulating 5-HT, DA and other signaling pathways. These findings demonstrated that SWHP produced an anxiolytic-like effect and the mechanism of action involves the serotonergic and dopaminergic systems, although underlying mechanism remains to be further elucidated.

Integrating serum pharmacochemistry and network pharmacology to reveal the active constituents and mechanism of Corydalis Rhizoma in treating Alzheimer's disease.

Background: Alzheimer's disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients for treating AD has attracted much attention. Corydalis rhizome (CR) is a traditional Chinese medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used for treating AD. However, no systematic study has been conducted to explore the anti-AD efficacy of CR, as well as its active compounds and mechanisms of action. Objective: The present study aimed to clarify CR's active constituents and its pharmacological mechanisms in treating AD. Methods: A D-galactose & scopolamine hydrobromide-induced AD mouse model was used and CR was administered orally. The prototypical alkaloid components were identified in the serum. The core components, key targets, and possible mechanisms of action of these alkaloids were revealed through network pharmacology. Molecular docking of the key target was performed. Finally, the mechanism was validated by lipopolysaccharide (LPS)-induced activation of BV2 microglia. Results: The results showed that CR improved anxiety-like behavior, spatial and non-spatial recognition, and memory capacity in AD mice. It also achieved synergistic AD treatment by modulating neurotransmitter levels, anti-neuroinflammation, and anti-oxidative stress. The core components that enhance CR's efficacy in treating AD are protoberberine-type alkaloids. The CR may induce the polarization of LPS-activated BV2 microglia from phenotype M1 to M2. This is partially achieved by modulating the IL-6/JAK2/STAT3 signaling pathway, which could be the mechanism by which CR treats AD through anti-inflammation. Conclusion: The present study provided a theoretical and experimental basis for the clinical application of CR in treating AD. It also provides information that aids the secondary development, and precise clinical use of CR.