Comprehensive online two-dimensional liquid chromatography coupled to hybrid linear ion trap Orbitrap mass spectrometry with optimized dilution and modulation for analysis of Huangqi Guizhi Wuwu decoction.

Huangqi Guizhi Wuwu decoction (HGWD), as a classical formula, has been used for thousands of years in China. In this work, a comprehensive strategy was proposed for characterizing the chemical profile of HGWD based on online two-dimensional hydrophilic interaction and reversed-phase liquid chromatography coupled with hybrid linear ion trap-Orbitrap mass spectrometry (online HILIC × RP-ESI/HRMS/MSn). The compounds in HGWD were first separated by the combined use of an XBridge amide column (150 × 4.6 mm, 3.5 µm) and Accucore C18 column (50 mm × 4.6 mm, 2.6 µm). Modulation with assistant technology, including trap columns and online dilution, was optimized and developed to decrease potential analyte loss and improve the resolution of the system. Subsequently, the accurate mass was determined by high-resolution Orbitrap and MSn fragment data by a hybrid linear ion trap (LTQ). In total, 170 chemical constituents were unambiguously identified or tentatively characterized in both positive and negative ion modes. Our study demonstrated that the proposed online HILIC × RP system coupled to the LTQ-Orbitrap MS platform is an efficient analytical technique for characterizing the chemical profile of multicomponent systems.

Neuroprotective Effect of Dichloromethane Extraction From Piper nigrum L. and Piper longum L. on Permanent Focal Cerebral Ischemia Injury in Rats.

BACKGROUND: Piper nigrum L. and Piper longum L. consist a classic formula in traditional Chinese Hui medicine and are widely used in treatment of stroke. To examine the therapeutic effect of neuron injury after apoplexy, we used a permanent middle cerebral artery occlusion model in rats to investigate the effects of dichloromethane fraction (DF) of Piper nigrum L. and Piper longum L. MATERIALS AND METHODS: After subjecting the rats to permanent middle cerebral artery occlusion, DF (100 and 200 mg/kg) were administered for 14 days. Neurological deficits and the degree of cerebral tissue injury was detected by 2,3,5-Triphenyltetrazolium Chloride Staining Hematoxylin and eosin staining and Nissl staining. Postsynaptic density protein 95 (PSD-95), synapsin-I (syn-I), and α-synuclein (α-syn) were stained by immunohistochemistry. PSD-95, Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMK II), phosphorylated CaMK II (p-CaMK II), CaM, N-methyl D-aspartate receptor subtype 2B (NR2B) expression were detected by Western blot. Meanwhile, phytochemical profile of DF was determined through ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). RESULTS: DF alleviated neurological deficits and markedly prevented ischemia-induced cellular damage. Immunohistochemical micrographs revealed that PSD-95 and syn-I proteins increased, and α-syn presented reduced expression in brain samples from the sham group. Western blot analyses revealed that the model group exhibited a noticeable reduction in PSD-95, p-CaMK II, CaM, and NR2B. The DF-treated model group exhibited increased PSD-95, p-CaMK II, CaM, and NR2B. UPLC-Q-TOF/MS analysis revealed eight main components of DF, of which piperine accounted for the largest proportion.

Quality evaluation for Radix Astragali based on fingerprint, indicative components selection and QAMS.

Radix Astragali (RA) is one of the most widely used Chinese herbs prescribed in many Chinese formulas to reinforce 'Qi' and treat vital energy deficiency. This study combined fingerprinting with quantitative analysis multi-components by a single marker (QAMS) to improve the quality control standard for RA on the basis of existing quality control methods of traditional Chinese medicinal materials. UPLC-ESI-TOF-MS technique was used to evaluate the quality of RA by fingerprinting and QAMS. Using the anti-inflammatory, anti-oxidation and anti-anoxic activities to screen characteristic components of RA, the calycosin-7-O-ß-d-glucoside (CG), ononin, astragaloside IV, astragaloside II, calycosin and astrageloside I significantly inhibited ear edema in mice, the calycosin and CG had good antioxidant activity and the astragaloside I had a significant anti-hypoxia activity. Astragaloside I, astragaloside II, astragaloside IV, ononin, calycosin and CG had significant pharmacological actions. These components were comprehensively used as the indicative components for the quality control of RA. Astragaloside I was used as the internal standard of the relative correction factors of CG (13.45), ononin (0.51), calycosin (12.08), astragaloside IV (0.73) and astragaloside II (0.81). Astragaloside I and CG were used as internal standards of the relative correction factors of the flavonoids and saponins of ononin (1.11), calycosin (0.04), astragaloside IV (0.73) and astragaloside II (0.81). The study combined fingerprinting with QAMS to improve the quality control standard for RA.

Total flavonoids of Chrysanthemum indicum L inhibit colonic barrier injury induced by acute pancreatitis by affecting gut microorganisms.

BACKGROUND: Acute pancreatitis (AP) is a prevalent acute abdominal condition, and AP induced colonic barrier dysfunction is commonly observed. Total flavonoids of Chrysanthemum indicum L (TFC) have exhibited noteworthy anti-inflammatory and anti-apoptotic properties. METHODS: We established AP models, both in animals and cell cultures, employing Cerulein. 16S rRNA gene sequencing was performed to investigate the gut microorganisms changes. RESULTS: In vivo, TFC demonstrated a remarkable capacity to ameliorate AP, as indicated by the inhibition of serum amylase, myeloperoxidase (MPO) levels, and the reduction in pancreatic tissue water content. Furthermore, TFC effectively curtailed the heightened inflammatory response. The dysfunction of colonic barrier induced by AP was suppressed by TFC. At the in vitro level, TFC treatment resulted in attenuation of increased cell apoptosis, and regulation of apoptosis related proteins expression in AR42J cells. The increase of Bacteroides sartorial, Lactobacillus reuteri, Muribaculum intestinale, and Parabacteroides merdae by AP, and decrease of of Helicobacter rodentium, Pasteurellaceae bacterium, Streptococcus hyointestinalis by AP were both reversed by TFC treatment. CONCLUSIONS: TFC can effectively suppress AP progression and AP induced colonic barrier dysfunction by mitigating elevated serum amylase, MPO levels, water content in pancreatic tissue, as well as curtailing inflammation, apoptosis. The findings presented herein shed light on the potential mechanisms by which TFC inhibit the development of AP progression and AP induced colonic barrier dysfunction.

Chitosan-based injectable hydrogel with multifunction for wound healing: A critical review.

Different types of clinical wounds are difficult to treat while infected by bacteria. Wound repair involves multiple cellular and molecular interactions, which is a complicated process. However, wound repair often suffers from abnormal cellular functions or pathways that result in unavoidable side effects, so there is an urgent need for a material that can heal wounds quickly and with few side effects. Based on these needs, hydrogels with injectable properties have been confirmed to be able to undergo self-healing, which provides favorable conditions for wound healing. Notably, as a biopolymer with excellent easy-to-modify properties from a wide range of natural sources, chitosan can be used to prepare injectable hydrogel with multifunction for wound healing because of its outstanding flowability and injectability. Especially, chitosan-based hydrogels with marked biocompatibility, non-toxicity, and bio-adhesion properties are ideal for facilitating wound healing. In this review, the characteristics and healing mechanisms of different wounds are briefly summarized. In addition, the preparation and characterization of injectable chitosan hydrogels in recent years are classified. Additionally, the bioactive properties of this type of hydrogel in vitro and in vivo are demonstrated, and future trend in wound healing is prospected.

Multi-functional chitosan-based nanoparticles for drug delivery: Recent advanced insight into cancer therapy.

Cancer therapy continues to be a major global concern, with conventional treatments suffering from low efficacy, untargeted drug delivery, and severe side effects. Recent research in nanomedicine suggests that nanoparticles' unique physicochemical properties can be leveraged to surmount the limitations of conventional cancer treatment. Chitosan-based nanoparticles have gained significant attention due to their high drug-carrying capacity, non-toxicity, biocompatibility, and long circulation time. Chitosan is utilized in cancer therapies as a carrier to accurately deliver active ingredients to tumor sites. This review focuses on clinical studies and current market offerings of anticancer drugs. The unique nature of tumor microenvironments presents new opportunities for the development of smart drug delivery systems, and this review explores the design and preparation of chitosan-based smart nanoparticles. Further, we discuss the therapeutic efficacies of these nanoparticles based on various in vitro and in vivo findings. Finally, we present a forward-looking perspective on the challenges and prospects of chitosan-based nanoparticles in cancer therapy, intending to provide fresh ideas for advancing cancer treatment strategies.

Systematic evaluation and meta-analysis of Chinese medicine in the treatment of centrally mediated abdominal pain syndrome.

BACKGROUND: This study aimed to evaluate the clinical efficacy of Chinese medicine for the treatment of centrally mediated abdominal pain syndrome (CAPS) using a meta-analysis system. METHODS: Six databases, including China National Knowledge Infrastructure, Vendor Information Pages, Chinese Biomedical Database, Wanfang, PubMed, and Embase were searched for randomized controlled trials related to the treatment of CAPS with traditional Chinese medicine. The bias risk assessment tool and RevMan5.3 software (Copenhagen, The Nordic Cochrane Centre, The Cochrane Collaboration) were used to conduct quality assessment and meta-analysis, and the GRADE grading system was used to evaluate the quality of evidence for outcome indicators. RESULTS: Fifteen articles were included in this study. Meta-analysis results showed that the treatment group was more effective in terms of the total effective rate (relative risk = 1.27; 95% confidence interval [CI], 1.19-1.34; P < .00001), Behavioral Rating Scale-6 pain score (mean difference [MD] = -0.79; 95% CI, -0.99 to -0.59; P < .00001), and traditional Chinese medicine (TCM) symptom score (MD = -1.74; 95% CI, -2.23 to -1.26; P < .00001) than the control group (P < .05). However, in terms of numerical rating scale pain score (MD = 0.79; 95% CI, -1.70 to 0.12; P = .09), the efficacy was comparable between the 2 groups, and the difference was not statistically significant (P > .05). In terms of verbal rating scale pain, depression, and anxiety scores, the data could not be combined due to inconsistent scoring criteria, and only descriptive analysis was performed. The results showed that the treatment group was slightly better than the control group in terms of relieving verbal rating scale pain and improving anxiety and depression (P < .05). CONCLUSION: Chinese medicine can effectively improve the pain and TCM clinical symptoms of patients with CAPS and relieve patients' anxiety and depression with fewer adverse effects, which has certain therapeutic advantages. However, because of the low methodological quality assessment of the included literature, the quality of GRADE evidence for outcome indicators is of mostly low and very low quality, the strength of recommendation is weak, and the credibility of the conclusion is average. More rigorous, larger sample, and higher-quality clinical trials are required to provide a higher level of evidence-based medicine for the development of TCM treatment standards for CAPS.

Cyclodextrin-based adsorbents for the removal of pollutants from wastewater: a review.

Water is a vital substance that constitutes biological structures and sustains life. However, water pollution is currently among the major environmental challenges and has attracted increasing study attention. How to handle contaminated water now mainly focuses on removing or reducing the pollutants from the wastewater. Cyclodextrin derivatives, possessing external hydrophilic and internal hydrophobic properties, have been recognized as new-generation adsorbents to exert positive effects on water pollution treatment. This article outlines recent contributions of cyclodextrin-based adsorbents on wastewater treatment, highlighting different adsorption mechanisms of cyclodextrin-based adsorbents under different influencing factors. The crosslinked and immobilized cyclodextrin-based adsorbents all displayed outstanding adsorption capacities. Particularly, according to specific pollutants including metal ions, organic chemicals, pesticides, and drugs in wastewater, this article has classified and organized various cyclodextrin-based adsorbents into tables, which could pave an intuitive shortcut for designing and developing efficient cyclodextrin-based adsorbents for targeted wastewater pollutants. Besides, this article specially discusses cost-effectiveness and regeneration performance of current cyclodextrin-based adsorbents. Finally, the challenges and future directions of cyclodextrin-based adsorbents are prospected in this article, which may shed substantial light on practical industrial applications of cyclodextrin-based adsorbents.

Study on the Spectrum-Effect Relationship of the Traditional Effect of Saponins in Glycyrrhiza uralensis Fisch.

Licorice is a traditional Chinese medicine that has been used for a long time in China and still in great use today. The effect of licorice on tonifying spleen and invigorating qi has been proved for thousands of years, but the material basis of its effect is not clear. In this paper, we established the fingerprints of 21 batches of licorice collected from different origins in China with High-Performance Liquid Chromatography (HPLC) to identify the common peaks. Its effect of tonifying spleen and invigorating qi was confirmed through a series of praxiology experiments. The spectrum-effect relationship between HPLC fingerprints and its effect of tonifying spleen and invigorating qi of licorice was examined by gray relational analysis and partial least squares regression analysis. Results showed that the effect of licorice on tonifying spleen and invigorating qi resulted from various compounds and peaks. X 2-X 6 is presumed to be the main pharmacological substance base. This research successfully identified the spectrum-effect relationship between HPLC fingerprints and the effect of licorice on tonifying spleen and invigorating qi. The research method based on the spectrum-effect relationship helps provide new research ideas and strategies for the study of the basis of the medicinal materials and quality control of traditional Chinese medicine.

Chemical and physical chitosan hydrogels as prospective carriers for drug delivery: a review.

With the advancement of medical research, the source and preparation of biological materials have gradually attracted attention. Hydrogels prepared from natural polysaccharides have been extensively applied in the medical field. The biocompatibility, excellent degradability and low toxicity of chitosan have favored the use of chitosan hydrogels as prospective carriers for drug delivery. Special chitosan hydrogels that effectively release target drugs based on different environmental stimuli have also been developed. This article reviews recent research progress in the development of chemical and physical chitosan hydrogels for drug delivery. In particular, preparation methods together with the chemical and physical properties of chitosan hydrogels are summarized. We also discuss multiple mechanisms of drug release from chitosan hydrogels. Finally, we highlight the future prospects of chitosan hydrogels in medical research.

Cyclodextrin-based delivery systems for chemotherapeutic anticancer drugs: A review.

Cancer is increasingly becoming a serious threat to human life and health. Therefore, the development of safe and effective therapeutic agents against the disease is of crucial significance. Cyclodextrins (CDs) are cyclic oligosaccharides obtained by the enzymatic hydrolysis of starch, and constitute a class of cyclic oligosaccharides with external hydrophilic and internal hydrophobic properties and have been used widely in cancer therapy. Cyclodextrin has been extensively applied in nanomedicine therapy, gene therapy, cell therapy, immunotherapy, and chemotherapy. In this review, we summarize chemotherapy drugs for cancer treatment, classify various CD-based drug delivery systems, and describe their chemotherapy release and cancer treatment performance. In addition, current challenges and new opportunities for CD-based chemotherapeutic agents delivery systems are discussed.

Spectrum-Effect Relationships of Flavonoids in Glycyrrhiza uralensis Fisch.

Glycyrrhiza uralensis Fisch. is used in large quantities in traditional Chinese medicine. It contains flavonoids, saponins, and polysaccharides, with flavonoids being the main active ingredients. In this study, flavonoids were isolated from the roots of Glycyrrhiza uralensis Fisch. grown in 21 areas in China by water extraction, alcohol precipitation, polyamide resin separation, and other methods. Fingerprints were established by high performance liquid chromatography (HPLC). There were 15 common peaks in the fingerprints by similarity evaluations of the chromatographic fingerprints. The spectrum-effect relationships between the HPLC fingerprints and pharmacological activities of flavonoids in G. uralensis Fisch., including the heat clearing, detoxifying effects, cough relief, and phlegm elimination effects, were assessed by gray relational analysis and partial least squares regression. After HPLC-quadrupole time-of-flight mass spectrometry and standard comparison, these five identified compounds (liquiritin apioside, neoisoliquiritin, licochalcone A, licochalcone B, and licochalcone C) could be used to evaluate licorice quality with regard to its efficacy. This research provides a scientific basis for improving licorice quality and also establishes a model for modernization of traditional Chinese medicines.

Dichloromethane extraction from Piper nigrum L. and P. longum L. to mitigate ischemic stroke by activating the AKT/mTOR signaling pathway to suppress autophagy.

Dichloromethane fraction (DF) of Piper nigrum L. and P. longum L. (PnL and PlL), has been found to exert a protective effect against ischemic stroke in rats. However, the regulatory mechanism exerted by PnL and PIL have not been fully elucidated. In this study, we found that DF greatly ameliorated cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion (pMCAO). The neurological score, behavioral assessment, brain infarct volume, phosphorylation of AKT (p-AKT), phosphorylation mTOR (p-mTOR), and Atg7 protein levels were determined. Additionally, we discovered that DF pretreatment reduced infarct volume, neurological score, and brain damage. Furthermore, DF therapy caused the downregulation of Atg7 and p-AKT expression, as well as the upregulation of p-mTOR expression. In conclusion, our findings indicated that DF treatment can reduce brain damage and inhibit apoptosis and autophagy by activating the Akt-mTOR signaling pathway in ischemic stroke.

Piperine as a neuroprotective functional component in rats with cerebral ischemic injury.

Long pepper (Piper longum L.) and black pepper (Piper nigrum L.) plants are commonly used as spices around the world and have also been postulated to have medicinal effects. Piperine, as the major alkaloid of P. nigrum and P. longum, has gained wide attention of the medical community and culinary enthusiasts. This study seeks to determine the effects of piperine on neuronal apoptosis in peri-infarcted cerebral cortices of rats with permanent middle cerebral artery occlusion (pMCAO) injury. Evaluation of the different behavioral components was conducted after pMCAO. 2, 3, 5-Triphenyltetrazolium chloride (TTC) was used to evaluate the area of cortical ischemia. Gross histopathological changes, as well as microscopic neuronal changes, were observed in brain tissue samples. The protein expression of Caspase-3, Caspase-9, Bax, Bcl-2, and Cytochrome C (Cyt-c) was analyzed using western blotting. The findings reveal that rats that received piperine treatment show markedly decreased neurological deficit, less ischemia-induced cellular damage, as well as smaller areas of cerebral infarction, with less severe macro and microcellular cerebral structural changes. Western blotting analysis reveals that piperine administration inhibits Bax, while enhancing Bcl-2 expression. The protein expression of Caspase-3, Caspase-9, and Cyt-c was also found to be significantly inhibited. We conclude that piperine may provide several beneficial neuroprotective effects that warrant further investigation.

The ethnopharmacology, phytochemistry and pharmacology of Angelica biserrata - A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica biserrata (R.H. Shan & C.Q. Yuan) C.Q. Yuan & R.H. Shan (Angelica pubescens Maxim. f. biserrata Shan et Yuan) (A.biserrata) is a widely used traditional Chinese medicine; its roots known as 'Duhuo' in China. The herb is used for expelling wind, eliminating dampness, and terminating pain. Moreover, it is used for treating the onset of anemofrigid-damp arthralgia, pain of the waist and knee and headache caused by latent wind pathogenic factor or damp-cold pathogenic factor. A.biserrata is slightly warm, bitter and pungent in taste, and it is well distributed in regions such as Sichuan and Hubei Provinces. AIM OF THE STUDY: This review aims to provide critical summary of the current evidence on A.biserrata. In particular, the progress of studies in the fields of botany, ethnopharmacology, phytochemistry, pharmacology and toxicity are discussed. Possible directions for future research are also briefly proposed. MATERIALS AND METHODS: Information on A.biserrata was collected from the internet database PubMed, Elsevier, China Knowledge Resource Integrated databases, ResearchGate, Web of Science, Wiley Online Library and Europe PMC using a combination of various relevant keywords. Other published books providing an overview of extant literature studies were considered for reference if they are related to the taxonomy, traditional knowledge, phytochemistry, pharmacology and toxicity of the plant. RESULTS: A substantial proportion of the isolated and identified compounds of the herb were reported to be coumarins and volatile oils. Biological effects, such as neuroprotective, anti-tumor, anti-arthritis, anti-inflammatory, and sedative, were also validated in In vitro and in vivo studies. Therapeutic effects are attributed to the bioactivities of the naturally occurring compounds in this herb. CONCLUSIONS: A.biserrata has been proven as a valuable medicinal sources from traditional herb. Some conventional uses has been evaluated by pharmacological investigation. Although the crude extracts of A.biserrata has been emerged to possess more pharmacological activities, it is now time to isolate and identify more active chemical constituents by Bioactivity-Guided and elucidate their structure-activity relationship. More designed investigations are need to focus on understanding the multi-target network pharmacology, clarity the molecular mechanism of action and efficacy as well as identifying the effective doses of A.biserrata. In addition, A.biserrata is not fully assessed regarding its safety. Further studies are essential to investigate its toxicity on human. It's useful to provide identify its underlying therapeutic remedy and economic value of developing new medicine in the future.

Ethnomedicine, Phytochemistry and Pharmacology of Smilax glabra: An Important Traditional Chinese Medicine.

Smilax glabra (SG) Roxb., a well-known traditional Chinese medicine, has been extensively used worldwide for its marked pharmacological activities for treating syphilitic poisoned sores, limb hypertonicity, morbid leucorrhea, eczema pruritus, strangury due to heat, carbuncle toxin, and many other human ailments. Approximately 200 chemical compounds have been isolated from SG Roxb., and the major components have been determined to be flavonoids and flavonoid glycosides, phenolic acids, and steroids. Among these active compounds, the effects of astilbin, which is used as a quality control marker to determine the quality of SG Roxb., have been widely investigated. Based on in vivo and in vitro studies, the primary active components of SG Roxb. possess various pharmacological activities, such as cytotoxic, anti-inflammatory and immune-modulatory effects, anti-oxidant, hepatoprotective, antiviral, antibacterial, and cardiovascular system protective activities. However, an extensive study to determine the relationship between the chemical compositions and pharmacological effects of SG Roxb. has not been conducted and is worth of our study. Improving the means of utilizing the effects of SG is crucial. The present paper reviews the ethnopharmacology, phytochemistry, and pharmacology of SG Roxb. and assesses its ethnopharmacological use in order to explore its therapeutic potential for future research.

Anti-inflammatory effect of Calycosin glycoside on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells.

Objective to find the Calycosin glycoside (CG) potential anti-inflammatory effect. The anti-inflammatory activity of CG was evaluated by lipopolysaccharide (LPS)-induced RAW 264.7 cells, and the IL-6, IL-1ß, TNF-α and PGE2 level were measured by ELISA; NO levels in the culture media were determined using the Griess reaction. The iNOS and COX-2 mRNA expressions were measured by qRT-PCR and the phosphorylation of IκBα, p65, ERK, JNK, and p38 was determined by western blotting. The CG could markedly inhibit the productions of NO and PGE2 and markedly inhibit the productions of TNF-α, IL-1ß and IL-6. CG could suppress mRNA expression of iNOS, COX-2 and protein phosphorylation of IκBα, p65, ERK, JNK, and p38 in LPS-induced RAW 264.7 cells. These findings indicate that CG exhibited potent anti-inflammatory activity through the NF-κB and MAPK signal pathway, and as a potential therapeutic agent against inflammatory diseases.