Matrix Gla protein and the long-term incidence and progression of coronary artery and aortic calcification in the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND AND AIMS: Matrix Gla protein (MGP) is an inhibitor of calcification that requires carboxylation by vitamin K for activity. The inactive form of MGP, dephosphorylated-uncarboxylated matrix Gla protein (dp-ucMGP), has been associated with increased calcification. However, it is not known whether there is a longitudinal relationship between dephosphorylated-uncarboxylated matrix Gla protein levels and coronary and aortic calcification in large population cohorts. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) followed participants with serial cardiac computed tomography (CT) measures of vascular calcification. Dp-ucMGP was measured at baseline in a subset of participants who completed baseline and follow-up CTs approximately 10 years later and had available plasma specimens (n = 2663). Linear mixed effects models (LMMs) were used to determine the association of dp-ucMGP with the simultaneous incidence and progression of coronary artery, ascending thoracic aortic, or descending thoracic aortic calcification (CAC, ATAC, DTAC)]. RESULTS: For every one standard deviation (SD, 178 pmol/L) increment in dp-ucMGP, CAC increased by 3.44 ([95% CI = 1.68, 5.21], p < 0.001) Agatston units/year (AU/year), ATAC increased by 0.63 ([95% CI = 0.27, 0.98], p = 0.001) AU/year, and DTAC increased by 8.61 ([95% CI = 4.55, 12.67], p < 0.001) AU/year. The association was stronger for DTAC in those ≥65 years and with diabetes. CONCLUSIONS: We found a positive association of the inactive form of matrix Gla protein, dp-ucMGP, and long-term incidence/progression of CAC, ATAC, and DTAC. Future studies should investigate dp-ucMGP as a calcification regulator and MGP as a possible therapeutic target to slow progression of calcification in the vasculature.

Research progress on ethnobotany, phytochemistry, pharmacological action, and applications of Engelhardia roxburghiana Wall: a review.

OBJECTIVES: Engelhardia roxburghiana Wall is a plant of the Juglandaceae family, and its leaves is the main part used as a medicine. It is used to relieve heat and pain, gasification, and dampness. The purpose of this review is to provide a systematic review about the botany, traditional uses, phytochemistry, pharmacology, and toxicology of this plant. KEY FINDINGS: Many compounds have been isolated and identified from the plant, including flavonoids, triterpenoids, steroids, quinones, essential oils, and other types of chemical constituents. Extensive pharmacological activities of the extracts or compounds of E. roxburghiana Wall in vivo and in vitro were mainly confirmed, including anti-cancer, anti-diabetic, anti-inflammatory, and anti-allergic effects. SUMMARY: In this paper, the botany, traditional uses, phytochemistry, and pharmacology of E. roxburghiana Wall were reviewed. In the future, E. roxburghiana Wall needs further study, such as paying more attention to quality control and the utilization on agriculture. In addition, discussing the medicinal components of decoction as well as the toxicity will also contribute to the progress of clinical trial studies.

Insights into Q-markers of honey-fried licorice in treating spleen deficiency based on substance and energy metabolism regulation.

BACKGROUND: Honey-fried Licorice (HFL) is a dosage form of Glycyrrhizae Radix et Rhizome processed with honey, which has been recorded to exhibit better efficacy in tonifying the spleen compared to the raw product. In contrast, different processing methods of Glycyrrhizae Radix et Rhizome exhibit different efficacies and applications, but their current quality control index components remain consistent. PURPOSE: Based on the discovery and research strategy of traditional Chinese medicine decoction piece quality marker (Q-marker), this study aimed to conduct a multidimensional integration of constituents absorbed into the body and metabolomics based on the tonifying spleen and stomach effects of HFL to effectively identify the Q-marker of HFL. METHODS: In this study, a spleen deficiency rat model was established using the "exhausted swimming + poor diet" method to investigate the pharmacodynamics of tonifying the spleen and stomach by HFL. The constituents absorbed into blood was conducted using UPLC-Q-TOF/MS, correlation analysis between metabolomics and constituents absorbed into blood recognized the Q-Marker of HFL. RESULTS: The pharmacodynamic data demonstrated that HFL exhibited a significant regulatory effect on the disordered levels of PP, trypsin, chymase, PL, α-Glu, MTL, GAS, VIP, IL-2, IFN-γ, and IgA in the spleen deficiency model. Furthermore, HFL was found to improve the pathological changes in the spleen and intestine in the spleen deficiency model, highlighting its significant "tonifying spleen and stomach" effect. In the serum containing HFL, a total of 17 constituents were identified as being absorbed into the blood. Among these, 11 were prototypical components, while 6 were metabolites. Metabolomics data revealed that 9 differentially expressed metabolic markers were observed. Furthermore, the analysis of endogenous metabolic markers indicated that 10 components exhibited significant correlations with these biomarkers. CONCLUSION: The effect of "tonifying spleen and stomach" of HFL is closely related to the regulation of the material and energy metabolism pathway. The Q-Marker of HFL is glycyrrhizic acid and 18ß-glycyrrhetinic acid as the main control standards and liquiritin, isoliquiritin, liquiritin, isoliquiritin, isolicorice flavonol, licorice chalcone C and Formononetin were used as auxiliary standards.

Tetrahydropiperine, a natural alkaloid with neuroprotective effects in ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a life-threatening neurological disease with various pathological mechanisms. Tetrahydropiperine (THP) is a natural alkaloid with protective effects against multiple diseases, such as seizure, and pain. This study was to examine the impact of THP on IS and investigate its potential mechanism. MATERIAL AND METHODS: We employed network pharmacology and molecular docking techniques to identify the target proteins of THP for intervention in IS. Adult male Sprague-Dawley rats were used to create a permanent middle cerebral artery occlusion model. PC-12 cells were chosen to establish an oxygen-glucose deprivation (OGD) cell model. Disease modeling followed by nimodipine (NIMO); 3-methyladenine (3-MA) and rapamycin (RAP) interventions. Open field test, Longa score, balance beam test, and forelimb grip test were used to measure motor and neurological functions. The degree of neurological damage recovery was assessed through behavioral analysis, and cerebral infarction volume was determined using TTC staining. Morphological changes were examined through HE and Nissl staining, and ultrastructural changes in neurons were observed using transmission electron microscopy. The protein expression of autophagy and related pathways was analyzed through Western blot (WB). The appropriate hypoxia time and drug concentration were determined using CCK-8 assay, which also measured cell survival rate. RESULTS: The network pharmacology findings indicated that the impact of THP on IS was enhanced in the PI3K/Akt signaling pathway. THP demonstrated robust docking capability with proteins associated with the autophagy and PI3K/Akt/mTOR, as indicated by the molecular docking outcomes. THP significantly improved behavioral damage, reduced the area of cerebral infarction, ameliorated histopathological damage from ischemia, increase neuronal survival, and alleviated ultrastructural damage in neurons (P < 0.05). THP enhanced the survival of PC-12 cells induced by OGD and ameliorated the morphological harm to the cells (P < 0.05). THP was found to elevate the quantities of P62, LC3-Ⅰ, PI3K, P-AKt/Akt, and P-mTOR/mTOR proteins while reducing the levels of Atg7 and Beclin1 proteins. The results of transmission electron microscopy showed no autophagosomes in the THP, 3-MA, and 3-MA + THP groups. CONCLUSION: The activation of the PI3K/Akt/mTOR signaling pathway by THP inhibits autophagy and provides relief from neurological damage in IS.

Isolation, phytochemistry, characterization, biological activity, and application of Morinda officinalis How oligosaccharide: a review.

Morinda officinalis How oligosaccharide (MOO) stands as one of the principal active constituents of M. officinalis How, widely employed in traditional Chinese medicine. The methods for MOO extraction predominantly encompass hot water extraction, ethanol extraction, ultrasonic-assisted extraction, and microwave-assisted extraction. Distinct extraction techniques yield varying MOO quantities. MOO encompasses a diversity of oligosaccharides, including bajijiasu, sucrose, 1-kestose, nystose, mannose, 1F-fructofuranosylnystose, 1,1,1,1-kestohexose, fructoheptasaccharide, inulin-type hexasaccharide, inulin-type heptasaccharide, inulotriose, inulotetraose, inulopentaose, and mannose. MOO exhibits a wide spectrum of biological activities, exerting specific effects on the nervous system, cardiovascular system, motor system, reproductive system, and immune system. It demonstrates antidepressant properties, offers potential in mitigating Alzheimer's disease, stimulates angiogenesis, and possesses anti-osteoporotic and other pharmacological effects. Clinically, when combined with various antidepressants, MOO exhibits specific therapeutic efficacy across multiple forms of depression. As a naturally occurring plant oligosaccharide, MOO holds diverse pharmaceutical applications. This article conducts a review of the latest extraction and purification methodologies, structural characterization analysis, biological activity assessment, and clinical applications of MOO. Such a comprehensive analysis yields innovative insights for advancing the research and application of MOO in the future.

The Anxiolytic Effect of Polysaccharides from Stellariae Radix through Monoamine Neurotransmitters, HPA Axis, and ECS/ERK/CREB/BDNF Signaling Pathway in Stress-induced Male Rats.

BACKGROUND: Stellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM) resource. Modern pharmacology has demonstrated the anti-anxiety effects of Stellaria dichotoma L. var. lanceolata Bge. polysaccharides (SDPs). SDPs are one of the active constituents of Stellaria dichotoma L. var. lanceolata Bge. This study presents the first extraction of SDPs and investigates their potential molecular mechanisms and anxiolytic effects that are not previously reported. METHODS: First, SDPs were obtained by water extraction and alcohol precipitation and analyzed for their monosaccharide composition by high performance liquid chromatography (HPLC). Male SD rats were subjected to a two-week indeterminate empty bottle stress procedure and a three-day acute restraint stress procedure, during which diazepam (DZP) (1 mg/kg) and SDPs (50, 100 and 200 mg/kg, intragastrically) were administered. A number of behavioral tests, including the elevated plus maze test (EPM), the open field test (OFT) and the light/dark box test (LDB), were used to assess the anti-anxiety potential of SDPs. Serum levels of Corticosterone (CORT) and Adrenocorticotropic hormone (ACTH), as well as the levels of Dopamine (DA) and serotonin (5-HT) found in the hippocampus and frontal cortex, were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In addition, protein levels of key proteins cAMP-response element binding protein (CREB), phospho-CREB (p-CREB), brain-derived neurotrophic factor (BDNF), ERK½, p-ERK½, and GAPDH expression in rat hippocampus were measured by Western blot analysis, and modulation of the endocannabinoid system was assessed by immunohistochemistry. RESULTS: Following administration of SDPs (50, 100, 200 mg/kg) and diazepam 1 mg/kg, anxiolytic activity was exhibited through an increase in the percentage of arm opening times and arm opening time of rats in the elevated plus maze. Additionally, there was an increase in the number of times and time spent in the open field center, percentage of time spent in the open box, and shuttle times in the LDB. Furthermore, tissue levels of DA and 5-HT were increased in the hippocampus and frontal cortex of rats after treatment with SDPs. In addition, SDPs significantly decreased serum levels of CORT and ACTH in rats. SDPs also effectively regulated the phosphorylation of the extracellular regulated protein kinases (ERK) and CREB-BDNF pathway in the hippocampus. Moreover, the expression levels of CB1 and CB2 proteins were heightened due to SDPs treatment in rats. CONCLUSIONS: The study verified that SDPs alleviate anxiety in the EBS and ARS. The neuroregulatory behavior is accomplished by regulating the Monoamine neurotransmitter, HPA axis, and ECB-ERK-CREB-BDNF signaling pathway.

Research Progress of Tamarixetin and its glycosides.

Tamarixetin and its glycosides are widely distributed in natural plants, and they are also natural flavonoid derivatives of quercetin. Its main pharmacological effects include antioxidant, anti-inflammatory, antiviral, anticancer, cardiovascular effects, etc. The pharmacokinetics showed that the distribution of direct absorption differed from that of biosynthesis. At the same time, research shows that tamarixetin is safe to use because it has little self-toxicity. In this paper, 181 articles on tamarixetin published from 1976 to 2023 are obtained from PubMed, China Knowledge Base Database, Wanfang Data, and other electronic databases. Tamarixetin is searched based on keywords, and 121 articles remain. Transformation synthesis, pharmacokinetics, pharmacological action, and structure-activity relationship of tamarixetin were reviewed.

Lack of Consensus Between Measurements of Plasma Phylloquinone by Enzyme-Linked Immunosorbent assays and a Well-Validated High-Performance Liquid Chromatographic Method.

Enzyme-linked i2mmunosorbent assays (ELISAs) that measure circulating phylloquinone have become commercially available, but their validity is uncertain. The objective of this study was to compare plasma phylloquinone concentrations measured using two commercially available ELISAs with concentrations measured using a validated high-performance liquid chromatography (HPLC) assay in 108 samples obtained from participants in a depletion (∼10 mcg phylloquinone/d)-supplementation (∼500 mcg phylloquinone/d) study. The geometric mean of plasma phylloquinone measured with ELISA A was 0.70 nmol/L, 37% lower than that measured with HPLC. The mean of the ELISA B measures was 12.4 nmol/L, >700% higher than the HPLC measures. Plasma phylloquinone measured using HPLC was significantly lower during phylloquinone depletion than supplementation (0.4 ± 0.1 compared with 1.2 ± 0.2 nmol/L; P < 0.001). Neither of the two ELISAs detected any significant difference in plasma phylloquinone concentrations between depletion and supplementation (ELISA A, P = 0.76; ELISA B, P = 0.29). These findings reinforce the need to validate plasma phylloquinone assays as they become available. Curr Dev Nutr 2023;x:xx.

Investigation of the Effects of Glabridin on the Proliferation, Apoptosis, and Migration of the Human Colon Cancer Cell Lines SW480 and SW620 and Its Mechanism Based on Reverse Virtual Screening and Proteomics.

Colon cancer is a relatively common malignant tumor of the digestive tract. Currently, most colon cancers originate from adenoma carcinogenesis. By screening various licorice flavonoids with anticancer effects, we found that glabridin (GBN) has a prominent anticolon cancer effect. First, we initially explored whether GBN can inhibit proliferation, migration, and invasion and induce apoptosis in SW480 and SW620 cells. Next, we exploited reverse virtual and proteomics technologies to screen out closely related target pathways on the basis of a drug and target database. At the same time, we constructed the structure of the GBN target pathway in colon cancer. We predicted that GBN can regulate the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-mammalian target of the rapamycin pathway (mTOR) pathway to fight colon cancer. Finally, through Western blot analysis and qRT-PCR, we verified that the expression levels of the PI3K, AKT, and mTOR proteins and genes in this pathway were significantly reduced after GBN administration. In short, the promising discovery of the anticolon cancer mechanism of GBN provides a reliable experimental basis for subsequent new drug development.

Effectiveness of adjuvant chemotherapy for elderly patients with triple-negative breast cancer.

There is little evidence determining whether elderly patients (from 70 to 90 years old) with triple-negative breast cancer could benefit from adjuvant chemotherapy (AC).  This study explores the effect of AC in these population following surgery. A total of 4610 patients were identified in the Surveillance, Epidemiology, and End Results database (2010-2018). Multiple imputation by chained equations was performed to impute missing data. Inverse probability of treatment weighting (IPTW) was applied to reduce the selection bias. IPTW-adjusted Kaplan-Meiers survival analysis and Cox proportional hazards models were performed to compare breast cancer specific survival (BCSS) and overall survival (OS) in the two treatment groups. The patients were classified into the chemotherapy (n=1989) and the observation (n=2621) groups. The percentage of patients receiving AC versus observation increased significantly from 2010 to 2018 (estimated annual percentage change, 1.49%; 95%CI, 0.75-2.16%, p=0.002). The 5-year IPTW-adjusted rates of BCSS and OS in AC group were better than that in observation group (BCSS: 82.32% vs. 78.42%, p=0.010; OS: 75.54% vs. 64.65%, p<0.001). The patients could benefit from AC based on the results of IPTW-adjusted Cox proportional hazards regression analysis (BCSS: HR, 0.77, 95%CI, 0.62-0.94, p=0.012; OS: HR, 0.66, 95%CI, 0.57-0.78, p<0.001). AC was associated with a significant outcome benefit across the year at diagnosis, marital status, stage, lymph node, surgery, and radiation subgroups (all p<0.050). Patients with T1ab could not benefit from AC (p>0.050). In conclusion, we presented a BCSS and OS benefit from AC in elderly patients with triple-negative breast cancer (TNBC). AC remained a reasonable treatment approach in these specific patients. For the patients with T1ab, de-escalated treatment would be administrated with caution.

Effects of dichloromethane extraction from Piper nigrum L. and P. longum L. on the expression of autophagy-related proteins in ischemic stroke.

Piper nigrum L. and P. longum L. are widely used in various medicinal formulations. The dichloromethane fraction of Piper nigrum L. and P. longum L. (DF) can prevent cerebral ischemic injury although the underlying mechanisms are obscure. The aim of this study was to evaluate the potential neuroprotective effects of DF on a rat model of permanent middle cerebral artery occlusion (pMCAO) and assess the molecular mechanisms. Animals were administered with DF (50, 100, and 150 mg/kg) or nimodipine (12 mg/kg) 6 h after pMCAO for 14 consecutive days via intragastric gavage. In the vitro this study identified that DF reduced neurological severity scores and improved survival rate. Results showed that DF markedly inhibited the percentage of apoptotic cells as well as neuronal autophagy and mitigated the overall neuronal and vascular damage in the ischemic region. Western blot testing showed that at the molecular level, DF significantly suppressed ischemia-induced activated expression of LC3, Beclin1, Atg12, and Atg5. Overall, our study indicated that DF attenuated neuronal autophagy by suppressing the expression of autophagy-related proteins to generate neuroprotection effect for ischemic stroke.

Brain vitamin D forms, cognitive decline, and neuropathology in community-dwelling older adults.

INTRODUCTION: Vitamin D purportedly protects against cognitive decline and dementia based on observational data using circulating 25-hydroxyvitamin D (25(OH)D). Little is known about vitamin D in the human brain and the association with dementia or neuropathology. METHODS: Decedents of the Rush Memory and Aging Project (n = 290) had vitamin D concentrations measured in four brain regions. Associations with cognitive and neuropathological outcomes were estimated using linear and logistic regression. RESULTS: The main form of vitamin D in all brain regions measured was 25(OH)D3 . Higher brain 25(OH)D3 concentrations were associated with a 25% to 33% lower odds of dementia or mild cognitive impairment (MCI) at the last visit before death (all P ≤ .031). However, brain 25(OH)D concentrations were not associated with any post-mortem neuropathology outcome studied. DISCUSSION: Higher brain 25(OH)D3 concentrations were associated with better cognitive function prior to death. Additional research is needed to clarify the specific mechanisms underlying this potentially protective relationship.

Inhibit progression of coronary artery calcification with vitamin K in hemodialysis patients (the iPACK-HD study): a randomized, placebo-controlled multi-center, pilot trial.

BACKGROUND: Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease. METHODS: A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest. RESULTS: A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups. CONCLUSION: We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.

Oncopreventive and Oncotherapeutic Potential of Licorice Chalcone Compounds: Molecular Insights.

BACKGROUND: Licorice is an important traditional Chinese medicine commonly used in clinical practice and contains more than 300 flavonoids. Chalcone is one of the main types of flavonoids with a wide range of biological functions and pharmacological activities. In the anticancer research, chalcone compounds have shown excellent performance. OBJECTIVE: This review aims to summarize the biosynthetic pathway and pharmacokinetics of chalcone from licorice and provide evidence for the anticancer effects of chalcone and the underlying mechanisms involved. METHODS: For this review, the following databases were consulted: the PubMed Database (https://pubmed.ncbi.nlm.nih.gov), Chinese National Knowledge Infrastructure (http:// www.cnki.net), National Science and Technology Library (http://www.nstl.gov.cn/), Wanfang Data (http://www.wanfangdata.com.cn/), and the Web of Science Database (http:// apps.webofknowledge.com/). RESULTS: To date, about 56 chalcones have been isolated and identified from licorice, 14 of which have antitumor effects. These chalcones have a wide range of biological activities and can inhibit the viability, proliferation, and migration of cancer cells by blocking the cancer cell cycle, thus inducing apoptosis and autophagy. However, the molecular mechanism of the anticancer effects of chalcone is not fully understood. CONCLUSION: In this paper, the molecular mechanism of chalcone regulating different types of cancer is reviewed in detail from the biosynthetic pathway. This comprehensive review article summarizes the biosynthetic pathway and pharmacokinetics of chalcone from the traditional Chinese medicine licorice and provides evidence for the potential anticancer effects of chalcone and the respective mechanisms of action. This paper also provides a basis for structural modification, biosynthesis, and new drug development of chalcone compounds in Glycyrrhiza uralensis.

Ethyl Acetate Extract from Artemisia argyi Prevents Liver Damage in ConA-Induced Immunological Liver Injury Mice via Bax/Bcl-2 and TLR4/MyD88/NF-κB Signaling Pathways.

BACKGROUND: Immunological liver injury (ILI) is a common liver disease and lacks potent drugs for treatment. Artemisia argyi Lévl. et Vant. (A. argyi), a medicinal and edible homologous plant usually used in diet therapy to cure various liver diseases, provides a great option for the prevention of ILI. PURPOSE: To investigate the effect that ethyl acetate extract of A. argyi (AaEA) on Concanavalin A (ConA)-induced ILI and the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. METHODS: The chemical components of AaEA were studied by LC-MS. In animal experiments, the positive control group was administrated diammonium glycyrrhizinate (DIG, 100 mg/kg), while different doses of AaEA groups (AaEA-H, AaEA-M, AaEA-L) were pretreated with AaEA 2.00, 1.00, and 0.50 g/kg, respectively, by intragastric for seven days, once every day. Then, ConA (12.00 mg/kg) was used through tail intravenous injection to establish the ILI model. The blood samples and livers were collected to test the degree of liver dysfunction, inflammation, oxidative stress, histopathological changes, and cell apoptosis. Real-time PCR and Western blotting analysis were used to explain the mechanism of regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. RESULTS: The way in which AaEA prevents liver damage in immunological liver injury (ILI) mice caused by ConA was investigated for the first time. Pretreatment with AaEA reduced the expression of ALT, AST, and inflammatory factors (TNF-α and IFN-γ). Meanwhile, AaEA also reduced MDA levels but upregulated the contents of IL-4, SOD, and GSH-px, alleviating oxidative stress induced by ILI. Western blotting and real-time PCR analysis demonstrated that AaEA could regulate the expression level and relative mRNA expression of key proteins on Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways. Finally, 504 components from AaEA were identified by LC-MS analysis, mainly including flavones, phenolic acids, and terpenoids with anti-inflammatory and liver protective activities, which highlights the potential of AaEA for diet treatment of ILI. CONCLUSION: AaEA can work against ConA-induced ILI in mice by regulating Bax/Bcl-2 and TLR4/MyD88/NF-κB signaling pathways, which has the potential to be a great strategy for the prevention of ILI.

Update on new trend and progress of the mechanism of polysaccharides in the intervention of Alzheimer's disease, based on the new understanding of relevant theories: A review.

Alzheimer's disease (AD), a neurodegenerative disease with insidious onset and progressive progression, is the main type of dementia. Currently, there is no specific cure for the disease. At the same time, a series of drug developments based on the classic theory, the Aß cascade hypothesis, have not completed phase III clinical trials, challenging the hypothesis. Polysaccharides obtained from natural products can be used in the treatment of AD, which has attracted academic attention due to its advantages of multi-target, multi-channel, no or modest side effects. The TCM syndrome type of AD is mainly "qi and blood deficiency, kidney essence deficiency", and the medicine is mainly used to replenish qi and blood, kidney and bone marrow. Thus, there has been extensive and in-depth research on polysaccharides obtained from tonic Chinese herbal medicine in China. Based on this background, this paper evaluated the effects and mechanisms of natural polysaccharides on AD by combing and screening English and related literature in recent 5 years and summarized the extraction process and structure-activity relationship of polysaccharides.

Pulsatilla chinensis (Bge.) Regel: A Systematic Review on Anticancer of Its Pharmacological Properties, Clinical Researches and Pharmacokinetic Studies.

Pulsatilla chinensis (Bge.) Regel (PC) is one of the most commonly used Chinese medicines and has a history of thousands of years. This article reviews the research results of anti-cancer activity and its mechanism of action obtained from experimental, clinical, pharmacokinetic and bioinformatic studies in recent years. A large number of studies have shown that PC exerts had anti-cancer effects on different types of tumor cells by inhibiting cell proliferation, inducing apoptosis, inhibiting cell cycle and energy metabolism, inducing autophagy, and inhibiting angiogenesis. The literature has shown that PC can trigger the expression of autophagy-related molecules, activate the mitochondrial apoptotic pathway, inhibit the phosphorylation of PI3K downstream factors, down-regulate the expression of glycolysis-related proteins, and regulate a series of cancer-related signal pathways and proteins. The molecular mechanisms involved in PC include signal pathways such as Notch, PI3K/AKT/m TOR, AKT/mTOR, and MEK/ERK. The article also discusses the derivatives of the active ingredients in PC, which greatly improved the anti-cancer effect. In conclusion, this review provides a comprehensive overview of the biological effects and mechanisms of PC against cancer. The analysis of the literature shows that PC can be used as a potential drug candidate for the treatment of cancer.

Saikosaponin B4 Suppression Cancer Progression by Inhibiting SW480 and SW620 Cells Proliferation via the PI3K/AKT/mTOR Pathway in Colon Cancer.

BACKGROUND: Colon cancer is a gastrointestinal malignancy with high incidence and poor prognosis. OBJECTIVE: Saikosaponin B4 (SSB4) is a monomeric component of the Traditional Chinese medicine (TCM), Bupleurum. The current study investigates the therapeutic effect and mechanisms of SSB4 in colon cancer. METHODS: The proliferation of two colon cancer cell lines, SW480 and SW620, were assessed using CCK8 and expression of regulatory molecules, including Bax, Caspase3, Caspase9, Cleaved Caspase3, Cleaved Caspase9 and Bcl2 by flow cytometry and Western blotting. RESULTS: Survival rates, assessed by CCK8, of SW480 and SW620 cells decreased significantly when the SSB4 concentration was in the range 12.5-50 µg/ml. Flow cytometry measurements indicated apoptosis rates of 55.07% ± 1.63% for SW480 cells and 33.07% ± 1.28% for SW620 cells treated with 25 µg/ml SSB4. Western blotting revealed upregulation of the proapoptotic proteins, Bax, Caspase3, Caspase9, Cleaved Caspase3 and Cleaved Caspase9, and downregulation of the anti-apoptotic protein, Bcl2, in the presence of SSB4. Network pharmacology and molecular docking predicted that the PI3K/Akt/mTOR pathway might be the main regulatory target for the antitumor effect of SSB4. Further Western blotting experiments showed that SSB4 downregulated (p < 0.01) expression of PI3K, Akt, mTOR and the phosphorylated proteins, P-PI3K, P-Akt and P-MTOR. Expression of PI3K, Akt and mTOR mRNA was found to be downregulated by SSB4 (P < 0.01) as the result of RT-PCR measurements. CONCLUSION: SSB4 is a potent anti-colon cancer agent. Its effects are likely to be mediated by suppression of the PI3K/AKT/mTOR pathway.

Hyperoside: A Review of Its Structure, Synthesis, Pharmacology, Pharmacokinetics and Toxicity.

Hyperoside is an active ingredient in plants, such as Hypericum monogynum in Hypericaceae, Crataegus pinnatifida in Rosaceae and Polygonum aviculare in Polygonaceae. Its pharmacologic effects include preventing cancer and protecting the brain, neurons, heart, kidneys, lung, blood vessels, bones, joints and liver, among others. Pharmacokinetic analysis of hyperoside has revealed that it mainly accumulates in the kidney. However, long-term application of high-dose hyperoside should be avoided in clinical practice because of its renal toxicity. This review summarises the structure, synthesis, pharmacology, pharmacokinetics and toxicity of hyperoside.

Piperine ameliorates ischemic stroke-induced brain injury in rats by regulating the PI3K/AKT/mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Piperine (PIP), a main active component isolated from Piper nigrum L., exerts neuroprotective effects in a rat model of ischemic stroke (IS). However, studies on the effects of PIP on neuroprotection and autophagy after IS are limited. AIM OF THE STUDY: This study aimed to prove the protective effects of PIP against brain IS and elucidate its underlying mechanisms. MATERIALS AND METHODS: Specific pathogen-free male Sprague-Dawley rats were selected to establish a permanent middle cerebral artery occlusion model. The experiment was randomly divided into six groups: sham group, model group, PIP intervention group (10, 20, and 30 mg/kg group), and nimodipine group (Nimo group, 12 mg/kg). Neurological function score, postural reflex score, body swing score, balance beam test, and grip strength test were used to detect behavioral changes of rats. The area of cerebral infarction was detected by TTC staining, and the number and morphological changes of neurons were observed by Nissl and HE staining. In addition, the ultrastructure of hippocampal dentate gyrus neurons was observed using a transmission electron microscope. Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway proteins and autophagy-related proteins, namely, Beclin1 and LC3, in the hippocampus and cortex. Cell experiments established an in vitro model of oxygen-glucose deprivation (OGD) with the HT22 cell line to verify the mechanism. The experiment was divided into five groups: control group, OGD group, OGD + PIP 20 µg/mL group, OGD + PIP 30 µg/mL group, and OGD + PIP 40 µg/mL group. CCK-8 was used to measure cell activity, and Western blot was used to measure the expression of PI3K/AKT/mTOR signaling pathway proteins and autophagy-related proteins (Beclin1 and LC3). RESULTS: Compared with the model group, the neurological function scores, body swing scores, and postural reflex scores of rats in the 10, 20, and 30 mg/kg PIP intervention groups and Nimo groups decreased, whereas the balance beam score and grip test scores increased (all p < 0.05). After 10, 20, and 30 mg/kg PIP and Nimo intervention, the cerebral infarction area of pMCAO rats was reduced (p < 0.01), and Nissl and HE staining results showed that the number of neurons survived in the 30 mg/kg PIP and Nimo intervention groups increased. Cell morphology and structure were significantly improved (p < 0.05). Most of the hippocampal dentate gyrus neurons and their organelles gradually returned to normal in the 30 mg/kg PIP and Nimo intervention groups, with less neuronal damage. The expression levels of p-mTOR, p-AKT, and p-PI3K in the hippocampus and cortex of the 30 mg/kg PIP and Nimo intervention groups decreased, whereas the expression level of PI3K increased (all p < 0.05). In addition, the expression level of autophagy-related proteins, namely, Beclin1 and LC3-II, in the 30 mg/kg PIP and Nimo intervention groups decreased (all p < 0.05). Results of CCK-8 showed that after 1 h of OGD, the 30 and 40 µg/mL PIP intervention groups had higher cell viability than the OGD group (p < 0.01). Western blot results showed that compared with the OGD group, the expression level of p-mTOR, p-AKT, and p-PI3K in the 30 and 40 µg/mL PIP intervention groups decreased, and the expression level of PI3K increased (all p < 0.05). Moreover, the expression level of autophagy-related proteins, namely, Beclin1 and LC3-II, in the 30 and 40 µg/mL PIP intervention groups decreased (all p < 0.05). CONCLUSIONS: This study shows that PIP is a potential compound with neuroprotective effects. PIP can inhibit the PI3K/AKT/mTOR pathway and autophagy. Its inhibition of autophagy is possibly related to modulating the PI3K/AKT/mTOR pathway. These findings provide new insights into the use of PIP for the treatment of IS and its underlying mechanism.