Graded nutritional interventions in patients with dysphagia after stroke: an assessment of the effectiveness of therapeutic strategies for different swallowing functions.

OBJECTIVE: To evaluate the efficacy of graded nutrition intervention strategy in improving patients with different degrees of impaired swallowing function after stroke. METHODS: According to the way of nursing, the patients were divided into two group. The main outcome measure was Kota swallowing index (WSI) score, and the secondary outcome was complications during the intervention. SF-36 scale was used to evaluate the improvement of quality of life before and intervention. RESULTS: The WSI score in the control group was 62.34 ± 10.23 at 1 week after treatment, 70.52 ± 13.45 at 6 weeks after treatment, and 80.48 ± 9.87 at 12 weeks after treatment, while that in the intervention group was 71.45 ± 9.68 at 1 week after treatment, 75.81 ± 11.78 at 6 weeks after treatment, and 84.12 ± 14.32 at 12 weeks after treatment. The WSI scores of the intervention group were significantly higher than those of the control group (t = 5.634, p < 0.001), suggesting better swallowing function of the patients The incidence of pulmonary infection, malnutrition and gastroesophageal reflux in the intervention group was significantly lower than that in the control group (p < 0.05). There was no significant difference in throat inflammation and dehydration between the two groups (p > 0.05). In addition, graded nutrition interventions significantly improved patients' quality of life, including dimensions of physical functioning, role physics, physical pain, and social functioning. CONCLUSION: Compared with conventional treatment, personalized graded nutrition intervention can significantly improve the swallowing function and reduce the pulmonary infection rate in patients with swallowing disorders after stroke.

Five new secondary metabolites from Aster tataricus.

Aster tataricus L.f. is highly valued for its rich reserves of bioactive compounds. Our research focused on the identification of previously unreported compounds found within the ethanol extract of A. tataricus. Through meticulous spectroscopic analyses and computational methods like NMR calculations and ECD, we successfully elucidated the structures of five novel compounds termed tatarisides A-E (1-5), alongside two known compounds (6, 7). The anti-inflammatory assays conducted yielded noteworthy results, particularly in relation to compounds 1 and 5. These compounds exhibited significant potential in inhibiting the release of NO in LPS-induced RAW 264.7 cells, as evidenced by their respective IC50 values of 17.81 ± 1.25 µM and 13.32 ± 0.84 µM. The discovery of these new compounds adds to the existing knowledge of A. tataricus's chemical composition and potential applications.

Phenolic constituents with antibacterial activity from Eleutherine bulbosa.

Eleutherine bulbosa (Mill.) Urb. is a medicinal and edible plant with various benefits for humans and animals. In this work, four new phenolic constituents (1-4), along with six known phenolic compounds (5-10) were obtained from the red bulbs of E. bulbosa. Their structures with absolute configurations were characterized by extensive spectroscopic analysis, combined with HR-ESI-MS and quantum mechanical electronic circular dichroism (ECD). Compounds 1 and 2 are novel homologous and heterodimers, respectively, featuring an unusual spiro ring system. All isolated phenolic constituents were tested for their antibacterial effects. The results revealed four phenolic compounds 1-3 and 7 showed moderate antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Escherichia coli with minimum inhibitory concentration (MIC) values ranging from 15.6 to 250.0 µg/mL.

[Multi-component content determination of Dracocephalum tanguticum by quantitative analysis of multi-components by single-marker].

This study aims to establish a method for the simultaneous determination of 7 active components in Dracocephalum tanguticum and to evaluate the quality of medicinal materials from different habitats. The method was established with high performance liquid chromatography(HPLC) and the gradient elution was performed with the mobile phase of acetonitrile-methanol-0.2% phosphoric acid solution at a column temperature of 35 ℃, an injection volume of 15 µL, and a flow rate of 0.6 mL·min~(-1). The detection wavelength was set as 215 nm. With rosmarinic acid as the internal reference, the relative correction factors and the content of other 6 components were calculated. The results were compared with those obtained with the external standard method. The results showed that the samples from Huangzhong county, Qinghai province had the best quality, with the highest content of p-hydroxybenzoic acid, cosmosiin, rosmarinic acid, oleanolic acid, and ursolic acid(9.29, 12.14, 6.02, 3.11, 17.67 mg·g~(-1) respectively). The samples from Chaya county, Tibet autonomous region ranked the second, with the highest content of betulin and betulinic acid(15.53, 7.17 mg·g~(-1), respectively). The method is accurate, reliable, and repeatable and suitable for the simultaneous determination of multiple components in D. tanguticum. The content of functional components varied in the samples from different producing areas and can be used as the indicator for the quality evaluation of medicinal materials.

Efficacy and Safety of Gabapentin in Improving Sleep Quality of Patients with Sensory Nervous System Diseases: A Meta-Analysis.

Context: Sensory nervous-system diseases are chronic diseases that injury or disease of the somatosensory nervous system causes. Sleep disorders usually accompany these diseases, and in turn, worsen their conditions and form a vicious circle that brings great difficulties in clinical treatment. Objective: The study intended to systematically evaluate the clinical efficacy and safety of gabapentin in improving the sleep quality of patients with sensory nervous-system diseases using a meta-analysis, so as to provide evidence-based medical evidence for clinical treatment. Design: The research team performed a comprehensive narrative review by searching the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal (VIP), WANFANG, Chinese Biomedical Database (CBM), PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases. The search terms included gabapentin, 1-(aminomethyl)-cyclohexaneacetic acid, gabapentin hexal, gabapentin-ratiopharm, sleep, and insomnia. Setting: The review took place in the Department of Neurology at the First People's Hospital of Linping District in Hangzhou, China. Outcome Measures: The research team extracted the data from the studies meeting the inclusion criteria and then transferred them into the Review Manager 5.3 software for meta-analysis. The outcome measures included scores: (1) for the improvement in the degree of sleep interference score; (2) for the improvement in sleep quality; (3) for the rate of poor sleep quality; (4) for the rate awakenings of >5 per night; and (5) for the incidence of adverse reactions. Results: The research team found eight RCTs with 1269 participants, including 637 participants in a gabapentin test group and 632 participants in the placebo control group. The meta-analysis showed that the decrease in the degree of sleep interference [mean deviation (MD) = -0.86, 95% CI: (-0.91, -0.82), P < .00001] and the improvement in sleep quality [odds ratio (OR) = 2.64, 95% CI: (1.90, 3.67), P < .00001] in gabapentin group were significantly higher than those in placebo group (P < .05), while the rate of poor sleep quality [OR = 0.43, 95% CI: (0.23, 0.79), P = .007] and the rate of > 5 night awakenings [OR = 0.01, 95% CI: (0.05, 0.70), P = .01] in gabapentin group were significantly lower than those in placebo group (P < .05). No statistically significant differences existed in the incidence of adverse reactions between the two groups. Conclusions: Gabapentin is safe and effective in improving the sleep quality of patients with sensory nervous-system diseases. Due to the limitations of sample size and types of diseases in the current study, the field needs multicenter, large-sample, and high-quality RCTs for further validation in the future.

Kaempferol induces mitochondrial dysfunction and mitophagy by activating the LKB1/AMPK/MFF pathway in breast precancerous lesions.

Kaempferol has been suggested to be an effective anticancer agent in several malignant tumors. However, its function and mechanisms in breast precancerous lesions remain largely elusive. Here, we showed that kaempferol induced excessive mitochondrial fission and mitochondrial damage with activated mitochondrial fission factor (MFF)-mediated dynamin-related protein (DRP) 1 mitochondrial translocation. As a result, the PTEN-induced putative kinase 1 (PINK1)/Parkin signaling pathway was activated, accompanied by excessive mitophagy and reduced mitochondrial mass in cells. We also revealed that kaempferol-induced lethal mitophagy contributed to inhibiting breast precancerous lesion growth in vitro and in vivo. Furthermore, we verified serine/threonine kinase 11 (STK11/LKB1)/AMP-activated protein kinase (AMPK) pathway deficiency in breast precancerous lesions. Moreover, LKB1/AMPK pathway reactivation by kaempferol was required for excessive mitochondrial fission and lethal mitophagy. Taken together, our findings shed new light on the molecular mechanisms related to breast cancer prevention by kaempferol and provide evidence for its potential clinical application.

[A new lignan glucoside from stems and branches of Rhododendron ovatum].

Ten lignans were isolated from the ethanol extract of stems and branches of Rhododendron ovatum through column chromatography over silica gel, ODS, Sephadex LH-20, and MCI-gel resin and semi-preparative RP-HPLC. The structures of all compounds were elucidated by extensive spectroscopic data analysis(UV, IR, HR-ESI-MS, ECD and NMR) as(-)-4-epi-lyoniresinol-9'-O-α-L-rhamnopyranoside(1),(+)-lyoniresinol-3α-O-α-L-rhamnopyranoside(2),(+)-5'-methoxyisolariciresinol-9'-O-α-L-rhamnopyranoside(3),(-)-lyoniresinol-3α-O-ß-D-glucopyranoside(4),(+)-lyoniresinol-3α-O-ß-D-glucopyranoside(5),(-)-4-epi-lyoniresinol-9'-O-ß-D-glucopyransoide(6), racemiside(7), neociwujiaphenol(8),(+)-syringaresinol(9), and homohesperitin(10). Among them, compound 1 was a new aryltetralin-type lignan. All the isolated lignans were tested for antioxidant activities in Fe~(2+)-cysteine induced rat liver microsomal lipid peroxidation in vitro, and compounds 8 and 9 showed antioxidant activities on the formation of malondiadehyde(MDA) in rat liver microsomes at 1×10~(-5) mol·L~(-1), with significant inhibitory rates of 75.20% and 91.12%, respectively.

Dawning public health services dogma: An indigenous Southwest Chinese perspective in managing hypertension-with or without the "BPHS"?

Background: To alleviate the rising mortality burden due to hypertension and other non-communicable diseases, a new public health policy initiative in 2009 called the Basic Public Health Services (BPHS). Program was introduced by the Chinese government. The goal of the study is to assess the feasibility and impact of a nationwide health care service-the "BPHS". Methods: From January to December 2021, a stratified multistage random sampling method in the survey was conducted to select 6,456 people from 8 cities/districts in Yunnan Province, China, who were above the age of 35 years. 1,521 hypertensive patients were previously aware of their high blood pressure status were matched to the BPHS program database based on ID number and then further divided into BPHS group and non-BPHS (control) group. The results of the current study are based on their responses to a short structured questionnaire, a physical examination, and laboratory tests. The association between BPHS management and its effect on the control of hypertension was estimated using multivariable logistic regression models. We evaluated the accessibility and efficacy of BPHS health care services by analyzing various variables such as blood pressure, BMI, lifestyle modification, anti-hypertensive drugs taken, and cardiovascular risk factors. Results: Among the 1,521 hypertensive patients included in this study, 1,011 (66.5%) were managed by BPHS programme. The multivariable logistic regression model demonstrated that the BPHS facilitated hypertension control (OR = 1.640, 95% CI: 1.237-2.175). A higher proportion of participants receiving lifestyle guidance from the BPHS management showed lowering of total cholesterol. In comparison to the non-BPHS group, those under BPHS management adhered better to antihypertensive medications either single drug (54.3%) or in combination (17.3%) of drugs. Additionally, we also noticed that urban areas with centralized and well-established digital information management system had better hypertension treatment and control. Conclusions: Nearly two-thirds of the hypertensive patients in Yunnan Province were included in BPHS management. The impact of the national BPHS program was evident in lowering risk factors for cardiovascular diseases, promoting healthy lifestyles, lowering blood pressure, increasing medication adherence, and the better control rate of hypertension.

ß-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation.

Breast carcinoma is a multistep progressive disease. Precancerous prevention seems to be crucial. ß-Boswellic acid (ß-BA), the main component of the folk medicine Boswellia serrata (B. serrata), has been reported to be effective in various diseases including tumors. In this work, we demonstrated that ß-BA could inhibit breast precancerous lesions in rat disease models. Consistently, ß-BA could suppress proliferation and induce apoptosis on MCF-10AT without significantly influencing MCF-10A. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that ß-BA may interfere with the metabolic pathway. Metabolism-related assays showed that ß-BA suppressed glycolysis and reduced ATP production, which then activated the AMPK pathway and inhibited the mTOR pathway to limit MCF-10AT proliferation. Further molecular docking analysis suggested that GLUT1 might be the target of ß-BA. Forced expression of GLUT1 could rescue the glycolysis suppression and survival limitation induced by ß-BA on MCF-10AT. Taken together, ß-BA could relieve precancerous lesions in vivo and in vitro through GLUT1 targeting-induced glycolysis suppression and AMPK/mTOR pathway alterations. Here, we offered a molecular basis for ß-BA to be developed as a promising drug candidate for the prevention of breast precancerous lesions.

The Chinese Herbal Formula Ruyan Neixiao Cream Inhibits Angiogenesis of Precancerous Breast Lesions via Regulation of Ras/Raf/MEK/ERK Signaling Pathway.

Ruyan Neixiao Cream (RUc) is a traditional Chinese herbal formula which can effectively inhibit the angiogenesis of breast precancerous lesions. In order to reveal the specific mechanism, we carried out experiments in vitro and in vivo. We found that the conditioned medium of MCF-10AT cells treated with RUc transdermal solution (RUt) could significantly inhibit the proliferation, migration, invasion, tube formation of HUVECs and the capillary formation of rat aortic rings. RUt may down-regulate the expression of VEGF, MMP2, and MMP9 in MCF-10AT medium by down-regulating miR-21 and up-regulating TIMP-3 and RECK. We further confirmed in rats that the microvascular density of precancerous lesions decreased significantly after external use of RUc, which may be related to the inhibition of Ras/Raf/MEK/ERK signaling pathway related proteins. Presumptively, RUc may inhibit the angiogenesis of breast precancerous lesions by inhibiting Ras/Raf/MEK/ERK signaling pathway, thus relieving the inhibition of miR-21 on TIMP-3 and RECK, then down-regulating the secretion of angiogenic factors.

Effects of diallyl trisulfide, an active substance from garlic essential oil, on structural chemistry of chitin in Sitotroga cerealella (Lepidoptera: Gelechiidae).

The environmental pollution, evolution of resistance, and risks to human and aquatic animal health associated with pesticide application have attracted much attention globally. Herein, we tested the capacity of diallyl trisulfide (DAT) from garlic essential oil to control the destructive stored-product pest, Sitotroga cerealella. The effects of DAT on the total content of cuticular chitin and structure of adults S. cerealella were evaluated. This study was the first to investigate changes in chitin structure in adults due to exposure to DAT through Fourier-transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and differential scanning calorimetry. The results of these analyses revealed that the cuticular chitin content of pests decreased after DAT treatment. DAT treatment also reduced thermal stability and crystallinity of chitin. These findings indicate that DAT is a potent biopesticide that is active against the moth, and establishes the basis for its use as an IPM and alternative to chitin synthesis inhibitors.

A polymeric nanoformulation improves the bioavailability and efficacy of sorafenib for hepatocellular carcinoma therapy.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Sorafenib (sfb) is widely used in clinics for advanced HCC therapy. However, the therapeutic efficacy of sfb is suboptimal due to its poor water solubility, low bioavailability, and side effects. Here, we employed a clinically safe polymer poly(ethylene glycol)-b-poly(lactic acid) (PEG-b-PLA) to prepare a nanoparticle (NP)-based sfb formulation (NP-sfb) and tested its antitumor effect in multiple HCC models. NP-sfb could achieve effective drug loading and remain stable under physiological conditions. NP-sfb could be taken up by HepG2, Hepa1-6, and H22 cells and could efficiently inhibit cell proliferation and/or promote cell apoptosis. In vivo studies indicated that NP-sfb showed significantly improved therapeutic efficacy compared with free-sfb at the same dose or even higher doses. Mechanistic studies demonstrated that NP-sfb not only inhibited tumor proliferation and angiogenesis but also stimulated the tumor microenvironment by reducing the infiltration of immunosuppressive myeloid cells and increasing the ratio of cytotoxic T cells. This study demonstrates that the NP-based formulation is a promising strategy to improve the clinical application of sfb.

Design, synthesis and evaluation of a baicalin and berberine hybrid compound as therapeutic agent for ulcerative colitis.

Structural modification of active natural compoundswhichwereoriginated fromTraditional Chinese Medicine (TCM) have showedgreat advantagesin thedevelopmentof new drugs. In TCM, "Huangqin-Huanglian" is a classic "medicine couple"thathas been used to treat intestinal diseases for thousands ofyears, while baicalinand berberine are the major active compoundsof Huangqin and Huanglianrespectively. Based onthis"medicine couple",wedesignedand synthesizeda newbaicalin and berberine hybrid compound (BBH).Its molecular structure wasconfirmedby spectroscopy.The antibacterial activity of BBH was detected in vitro.Results indicatedthat the new hybrid compound exhibited the best antibacterial activity forproteobacteria as compared with its original synthetic materials (baicalin andberberine). In vivo, the effect of BBHon ulcerative colitiswas alsoinvestigated.BBH treatment significantly ameliorated the disease symptoms andpreventedthe colon damage of ulcerative colitis. Furthermore, BBH showed asignificant anti-inflammatory effect through regulating activities of SOD, MPOandexpressions of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in colontissue. Data also suggested that BBH was more superior than baicalin and berberine inameliorating colonic damage. This indicated that the new hybrid compound BBHshowed enhanced efficacy in treating ulcerative colitis.

Highly efficient synthesis and monoamine oxidase B inhibitory profile of demethyleneberberine, columbamine and palmatine.

The biosynthesis of berberine alkaloids is thought to begin with the demethylation of berberine followed by methylation reactions to generate other type berberine alkaloids. This seemingly expeditious way to access berberine alkaloids has been stagnated for over half a century due to certain vexing synthetic problems, such as low isolated yield, complex operations and toxic reagents. We further investigated this bioinspired semi-synthesis strategy and significantly improved the synthetic efficacy, by providing a practical synthetic process for demethyleneberberine (DMB), columbamine and palmatine. Furthermore, we found that DMB (IC50, 9.06 µM) inhibited the activity of monoamine oxidase B (MAO-B), an enzyme that deaminates dopamine and is particularly involved in the pathology of Parkinson's disease. Besides, columbamine was able to decrease MAO-B activity by approximately 40%. These findings provide perquisites for further in vivo investigation to confirm the therapeutic potentiality of berberine alkaloids, DMB in particular.

CuS-NiS2 nanomaterials for MRI guided phototherapy of gastric carcinoma via triggering mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

Gastric carcinoma is one of the most lethal malignant tumors. As part of our long-term efforts on seeking effective diagnosis and therapeutic strategies of gastric cancer, we present herein novel ternary copper-based chalcogenide nanoplatform CuS-NiS2 nanomaterials with outstanding photothermal (PT)/photodynamic (PD) property that could effectively suppress human gastric cancer in vitro and in vivo without obvious side effects. We revealed that CuS-NiS2 induced reactive oxygen species (ROS) generation, leading to apoptosis through Bcl-2/Bax pathway of human gastric cancer cells under 808 nm near-infrared (NIR) irradiation. In addition, we also confirmed that the combination of CuS-NiS2 and 808 nm NIR laser treatment triggered necroptosis by regulating the novel pathway MLKL/CAPG of human gastric cancer cells. Moreover, the CuS-NiS2 exhibited excellent contrast enhancement according to magnetic resonance imaging (MRI). Taken together, we reported new ternary copper-based chalcogenide nanomaterials CuS-NiS2, which could be successfully applied for MRI-guided PT/PD therapy of gastric carcinoma through mitochondria-mediated apoptosis and MLKL/CAPG-mediated necroptosis.

Aloe-Emodin Induces Breast Tumor Cell Apoptosis through Upregulation of miR-15a/miR-16-1 That Suppresses BCL2.

PURPOSE: Aloe-emodin (AE) is a natural compound derived from aloe vera and palmatum rhubarb and shows anticancer activities in various cancers. Bcl-2 family is the main regulator of cell death or cell survival. This study describes the effects of AE on proliferation of breast tumor (BT) cells. METHODS: MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 cell lines were exposed to AE. Cell proliferation and apoptosis were assessed by CCK-8 and flow cytometry. Protein levels were measured by Western blotting. The levels of mRNA and miRNA were examined by RT-PCR. Bioinformatics was applied to screen miRNAs that bind to 3'-UTR of mRNA. RESULTS: The results showed that AE selective activity inhibited the proliferation and induced apoptosis of MCF-10AT and MCF-7 cells but exhibited no significant inhibition in MCF10A and MDA-MB-231 cells. Mechanistically, AE dose-dependently decreased the protein expression of Bcl-2 and Bcl-xl, while it increased Bax protein expression in MCF-10AT and MCF-7 cells. The levels of Bcl-xl and Bax mRNA were altered by AE treatment, which was consistent with the protein expression results. However, Bcl-2 mRNA levels were not affected in either cell line, suggesting that AE may modulate the protein translation of Bcl-2 through miRNAs. In all candidate miRNAs that bind to 3'-UTR of Bcl-2, miR-15a and miR-16-1 were dose-dependently downregulated by AE. Moreover, inhibition of miR-15a/16-1 could eliminate the inhibition of MCF-10AT and MCF-7 cells growth by AE and could reverse the downregulation of AE-induced Bcl-2 protein level. CONCLUSION: Our research provides an important basis that AE induces BT cell apoptosis through upregulation of miR-15a/miR-16-1 that suppresses BCL2.

Pluronic-based graphene oxide-methylene blue nanocomposite for photodynamic/photothermal combined therapy of cancer cells.

A nanocomposite containing methylene blue (MB), graphene oxide (GO) and Pluronic F127 (PF127) had been developed for combined photothermal therapy (PTT) and photodynamic therapy (PDT). In this study, GO was firstly loaded with MB to form GO-MB by a self-assembly method, and then the surface was modified with PF127 to form GO-MB/PF127 nanocomposite (GO-MB/PF127) by a thin-film hydration method. The structure and properties of the nanocomposite were characterized by Ultraviolet-Visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, transmission electron microscope (TEM), dynamic light scattering (DLS) and zeta potential. The results showed that the as-prepared nanocomposite exhibited high stability in aqueous solution, high release rate of MB from the nanocomposite under acidic conditions. In addition, when excited by 808 nm near infrared (NIR) light and 660 nm light emitting diode (LED) source, GO in GO-MB/PF127 caused photothermal ablation of cancer cells while MB produced singlet oxygen (1O2) to kill cancer cells through oxidative stress in PDT. The combined therapy had a synergistic effect and can achieve a strong killing effect on SiHa cells at a low dose of GO-MB/PF127 containing GO (10 µg mL-1) and MB (5 µg mL-1). And PF127 did not affect the photothermal heating of GO and the 1O2 generation of MB. Moreover, light-induced GO-MB/PF127 nanocomposite killed SiHa cells by apoptosis pathway. The results indicated that the nanocomposite had the potential to effectively treat cancer via noninvasive phototherapy, and could be served as a multifunctional therapeutic agent for photodynamic/photothermal cancer therapy.

A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Paeonia lactiflora Pall. On the Treatment of Alzheimer's Disease.

OBJECTIVE: To investigate the potential active compounds and underlying mechanisms of Paeonia lactiflora Pall. (PLP) on the treatment of Alzheimer's disease (AD) based on network pharmacology. METHODS: The active components of PLP were collected from Traditional Chinese Medicine System Pharmacology (TCMSP) database, and their possible target proteins were predicted using TCMSP, SwissTargetPrediction, and STITCH databases. The putative AD-related target proteins were identified from Therapeutic Target Database (TTD), GeneCards, and MalaCards database. The compound-target-disease network interactions were established to obtain the key targets about PLP acting on AD by network topology analysis. Then, the function annotation and signaling pathways of key targets were performed by GO and KEGG enrichment analysis using DAVID tools. Finally, the binding capacity between active ingredients and key targets was validated by molecular docking using SystemsDock tools. RESULTS: There were 7 active compounds involving in 151 predicted targets identified in PLP. Besides, a total of 160 AD-related targets were identified. Among these targets, 30 shared targets of PLP and AD were acquired. After topological analysis of the PLP potential target-AD target network, 33 key targets that were highly responsible for the therapeutic effects of PLP on AD were obtained. Further GO and KEGG enrichment analysis showed that these key targets were significantly involved in multiple biological processes and pathways which participated in cell apoptosis and inflammatory response and maintained the function of neurons to accomplish the anti-AD activity. The molecular docking analysis verified that the 7 active compounds had definite affinity with the key targets. CONCLUSIONS: The ameliorative effects of PLP on AD were predicted to be associated with regulating neural cell apoptosis, inflammatory response, and neurotrophy via various pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, and neurotrophin signaling pathway.

A combined molecular biology and network pharmacology approach to investigate the multi-target mechanisms of Chaihu Shugan San on Alzheimer's disease.

Chaihu Shugan San (CSS) is a well-known herbal formula used to nourish liver and blood, promote blood circulation and Qi flow in Traditional Chinese Medicine. Modern pharmacological studies and clinical uses showed that CSS could ameliorate cognitive dysfunction of Alzheimer's disease (AD). The present study aimed to elucidate the multi-target mechanisms of CSS on AD using network pharmacology analysis and verify its effect by biological experiments. Firstly, a total of 152 active compounds in CSS, 520 predicted biological targets and 160 AD-related targets were identified. Subsequently, the networks including herb-compound-target network, AD-target network, and CSS potential target-AD target network were constructed. 60 key targets highly responsible for the beneficial effect of CSS on AD were identified by central network topological analysis. They were significantly characterized as nuclear or cytoplasmic proteins with molecular function of protein binding. They were also enriched in various biological processes through PI3K-Akt signaling pathway, MAPK signaling pathway and HIF signaling pathway by GO function and KEGG pathway enrichment analysis. Pretreatment with CSS ameliorated Aß-induced neural cell death and reduced the number of apoptotic cells in differentiated PC12 cells. Moreover, increased phosphorylation of Akt accompanied with decreased Bax expression was found after CSS pretreatment, suggesting that Akt signaling pathway was involved in the protective effect of CSS against neural cells death. The present study systematically revealed the multi-target mechanisms of CSS on AD using network pharmacology approach, as well as validated the protective effect of CSS against Aß-induced neural cells death through Akt signaling pathway. It provided indications for further mechanistic studies and also for the development of CSS as a potential treatment for AD patients.

A novel berberine-metformin hybrid compound exerts therapeutic effects on obese type 2 diabetic rats.

In this study, we investigated the biological activities of a novel berberine-metformin hybrid compound (BMH473) as an anti-diabetic agent. BMH473 exhibited significant anti-hyperglycaemic and anti-hyperlipidaemic effects on T2DM rats. In white adipose tissue, BMH473 reduced the perirenal and epididymal adipose tissue mass and modulated the lesions in perirenal adipose tissue, by inhibiting the protein expressions of PPAR-Ɣ, C/EBP-α and SREBP-1c as well as the mRNA expressions of lipogenic genes. Moreover, BMH473 downregulated the levels of pro-inflammatory cytokines in perirenal adipose tissue through the suppression of p-NF-κB. In liver, BMH473 reduced liver ectopic fat accumulation, by regulating the protein expression levels of SREBP-1c and PPAR-α as well as the mRNA expression levels of lipogenic genes. In addition, BMH473 inhibited hepatic gluconeogenesis by promoting the phosphorylation levels of AMPK α and ACC, and down-regulating the mRNA expression levels of FBPase, G6Pase and PEPCK. Furthermore, BMH473 exhibited significant inhibitory effects on lipogenesis and lipid accumulation in 3T3-L1 adipocytes by modulating the protein expression levels of PPAR-Ɣ, C/EBP-α and SREBP-1 c as well as the mRNA expression levels of lipogenic genes. In conclusion, our results suggest that the newly synthesized BMH473 is beneficial for maintaining glucose and lipid homeostasis in type 2 diabetic rats, and exhibits better anti-hyperlipidaemic effects compared to metformin and berberine.