Qualitative analysis of licorice and strychnine decoction before and after combination using UPLC-QE-Orbitrap-MS.

BACKGROUND AND OBJECTIVE: Glycyrrhiza glabra L. (GG) and Strychnos nux-vomica L. (NV) are traditional Chinese medicines (TCMs). Changes in the chemical composition may occur before and after the GG-NV compatibility. Ultra-performance liquid chromatography Q-exactive Orbitrap mass spectrometry (UPLC-QE-Orbitrap-MS) was applied here to study the difference in the components of the GG and NV decoctions before and after they were combined. The changes in the chemical composition of GG and NV before and after the combination were determined. METHODS: The precise molecular weight, retention time, and fragment ion peak of the different components of the decoctions before and after compatibility were obtained through UPLC-QE-Orbitrap-MS. Differential analysis methods, such as principal component analysis, were used for comparison. RESULTS: In the positive ion mode, 200 new components were added, whereas six components were lost. In the negative ion mode, 144 new compounds were identified, whereas three components were missing. CONCLUSIONS: The compatibility difference between GG and NV was studied through UPLC-QE-Orbitrap-MS. The chemical composition of GG and NV changed before and after compatibility, and a class of compounds different from GG and NV was identified in the co-decoction. This study provides an experimental basis for subsequent research into detoxification mechanisms of the GG-NV combination and offers a new analytical method for investigating the compatibility of various other TCM pairs.

Research Progress in the Field of Gambogic Acid and Its Derivatives as Antineoplastic Drugs.

Gambogic acid (GA) is a natural product with a wide range of pharmacological properties. It plays an important role in inhibiting tumor growth. A large number of GA derivatives have been designed and prepared to improve its shortcomings, such as poor water solubility, low bioavailability, poor stability, and adverse drug effects. So far, GA has been utilized to develop a variety of active derivatives with improved water solubility and bioavailability through structural modification. This article summarized the progress in pharmaceutical chemistry of GA derivatives to provide a reference and basis for further study on structural modifications of GA and expansion of its clinical applications.

Hyaluronic acid-coated nanostructured lipid carriers for loading multiple traditional Chinese medicine components for liver cancer treatment.

This study aimed to develop hyaluronic acid (HA)-coated nanostructured lipid carriers (NLC) loaded simultaneously with oleanolic acid (OA), ursolic acid (UA) and Ginsenoside Rg3 (Rg3), prepared by electrostatic attraction for delivering OA, UA and Rg3 (OUR), termed HA-OUR-NLC, to tumors over expressing cluster determinant 44(CD44). The dialysis method was used to assess the in vitro release of OUR. Parameters such as pharmacokinetics, biodistribution, fluorescence in vivo endo-microscopy (FIVE), optical in vivo imaging (OIVI) data, and in vivo antitumor effects were evaluated. The results showed a total drug loading rate of 8.76±0.95% for the optimized HA-OUR-NLC; total encapsulation efficiency was 45.67±1.14%; particle size was 165.15±3.84%; polydispersity index was 0.227±0.01; zeta potential was -22.87±0.97 mV. Drug release followed the Higuchi kinetics. Pharmacokinetics and tissue distribution, as well as antitumor effects were evaluated in nude mice in vivo. HA-OUR-NLC were better tolerated, with increased antitumor activity compared with 5-Fu. In in vivo optical imaging, we use 1,1'-dioctadecyl-3,3,3',3'-tetramethy(DiR) as a fluorescent dye to label the NLC. The DiR-OUR-NLC group showed bright systemic signals, while the tumor site was weak. The present findings indicated that HA-OUR-NLC accumulated in the tumor site, prolonging OUR duration in the circulation and enhancing tumoral concentrations. Therefore, NLC prepared by electrostatic attraction constitute a good system for delivering OUR to tumors.

Screening anaphylactoid components of Shuang Huang Lian Injection by analyzing spectrum-effect relationships coupled with UPLC-TOF-MS.

Shuang Huang Lian Injection (SHLI) has been used in China for over 30 years as an effective and widely used Chinese herbal prescription to treat acute respiratory infectious. SHLI has, however, caused many severe anaphylactoid reactions. It is important to identify the potential anaphylactoid components of SHLI. Spectrum-effect relationships were used to explore potentially anaphylactoid components. Based on the original herbal formula, honeysuckle, Fructus Forsythiae and Radix Scutellariae extracts were prepared and combined in appropriate proportions. The preparations were then injected into the caudal vein of rats to obtain in vivo serum samples for pharmacological evaluation and fingerprint analysis. The release rate of ß-hexosaminidase from RBL-2H3 cells and plasma histamine level was used as the pharmacological index. Chromatographic fingerprint analysis identified 22 common peaks. Regression analysis and correlation analysis were used to calculate the relationships between the peaks and the pharmacological effects and identified peaks 5, 6, 11, 12 and 17 as likely anaphylactoid agents. The correlated peaks were identified by comparing the fingerprints with in vitro samples and reference standard samples and the structure was identified by UPLC-TOF-MS. This study established a prospective method to clarify the anaphylactoid components in SHLI, which would provide guidances for screening anaphylactoid components in other traditional Chinese medicine injections.

[Pharmacological effect of combined administration of natures, tastes and components of Chinese herbal compounds].

The combined administration of traditional Chinese medicine (TCM) aims at comprehensive adjustment of body based on the theory of TCM and the theory of Chinese medicine property. The natures and tastes of TCM are the core of the theory of TCM property. The combined administration of natures and tastes of TCM is one of the important theories of prescription compatibility. The objective of study on the combined administration of natures and tastes of prescriptions according to symptoms of disease is to clarify the compatibility mechanism of prescriptions. The study on the compound compatibility of TCM under the guidance of theory of TCM focuses on the relationship between the composition, dosage and compatibility of TCM by using modern high-tech means. It demonstrates the effective combination of TCM theory and modern technology, and the inheritance and innovation of TCM theory. The study of the effect and mechanism of compatibility of natures and tastes of TCM under the guidance of TCM theory is helpful for the analysis of the compatibility effect and mechanism of TCM based on the pharmacological effect of natures and tastes of TCM. The correlation between the pharmacological effect of natures and tastes of TCM and the pharmacological effect of components were studied by modern informatics, which is beneficial to promote the development of theory of TCM compound. The study of the compatibility between natures, tastes and component of TCM shall pay attention to the combination of pharmacological effects of natures, tastes and component of TCM, so as to define the scientific connotation of the compatibility of TCM, and make full use of the characteristics and advantages of TCM. The methods and pharmacological effects of the combined administration of TCM compounds are reviewed to provide the theoretical basis for the development of new drugs and clinical application.

New Glycosides from the Fruits of Nicandra physaloides.

Three new glycosides (1-3) and 15 known ones (4-18) were isolated and identified from the fruits of Nicandra physaloides. The structures of these compounds were established by 1D and 2D NMR spectra and HR-ESI-MS. The compounds (4-18) were the first time isolated from the Nicandra genus and they (except 8, 10, 14) exhibited inhibitions on the NO release of LPS-induced RAW 264.7 cells with IC50 values from 26.9 to 47.5 µM.

Preparation, in vitro and in vivo evaluation of mPEG-PLGA nanoparticles co-loaded with syringopicroside and hydroxytyrosol.

This study investigated the therapeutic efficiency of monomethoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA) co-loaded with syringopicroside and hydroxytyrosol as a drug with effective targeting and loading capacity as well as persistent circulation in vivo. The nanoparticles were prepared using a nanoprecipitation method with mPEG-PLGA as nano-carrier co-loaded with syringopicroside and hydroxytyrosol (SH-NPs). The parameters like in vivo pharmacokinetics, biodistribution in vivo, fluorescence in vivo endomicroscopy, and cellular uptake of SH-NPs were investigated. Results showed that the total encapsulation efficiency was 32.38 ± 2.76 %. Total drug loading was 12.01 ± 0.42 %, particle size was 91.70 ± 2.11 nm, polydispersity index was 0.22 ± 0.01, and zeta potential was -24.5 ± 1.16 mV for the optimized SH-NPs. The nanoparticle morphology was characterized using transmission electron microscopy, which indicated that the particles of SH-NPs were in uniformity within the nanosize range and of spherical core shell morphology. Drug release followed Higuchi kinetics. Compared with syringopicroside and hydroxytyrosol mixture (SH), SH-NPs produced drug concentrations that persisted for a significantly longer time in plasma following second-order kinetics. The nanoparticles moved gradually into the cell, thereby increasing the quantity. ALT, AST, and MDA levels were significantly lower on exposure to SH-NPs than in controls. SH-NPs could inhibit the proliferation of HepG2.2.15 cells and could be taken up by HepG2.2.15 cells. The results confirmed that syringopicroside and hydroxytyrosol can be loaded simultaneously into mPEG-PLGA nanoparticles. Using mPEG-PLGA as nano-carrier, sustained release, high distribution in the liver, and protective effects against hepatic injury were observed in comparison to SH.

Phase Preparation of Xiao-chai-hu Decoction and its Pharmacodynamics of Acute Liver Injury.

BACKGROUND: Self-emulsifying nano-phase of traditional Chinese medicine are a research hotspot. Xiao-Chai-Hu decoction is a commonly used compound decoction in clinical practice, which is of great research significance. The aim of this study was to isolate and characterize the self-emulsifying nano-phase and other phases of Xiao-Chai-Hu decoction, and to study the effects of each phase on acute liver injury. METHODS: The liquid medicine was prepared employing centrifugation followed by dialysis. Single- factor investigation methodology was utilized to optimize the preparation parameters for both phases. Characterization of the formulated phase involved analyses such as surface morphology assessment, measurement of nanoparticle size and Zeta potential using an analyzer, observation of the Tyndall effect, conducting diffusion and dilution tests, examination under a microscope, and structural visualization via transmission electron microscopy (TEM). Furthermore, an acute liver injury model was established in rats through intraperitoneal injection of D-Galactosamine (D-Gal- N). To assess hepatic function and oxidative stress status, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in liver tissue were quantified. The liver coefficients for each group were calculated as an additional parameter. For histopathological evaluation, liver tissue sections from the experimental group were stained with Hematoxylin and Eosin (H&E) and examined microscopically under light conditions. These revisions aim to enhance clarity, correct minor grammatical errors (such as capitalization of "HE" to "H&E"), and ensure a smoother flow of information without altering the scientific content of your original text. RESULTS: Successful establishment and separation of four distinct phases were achieved, including the self-emulsifying nano-phase, precipitation phase, suspension phase, and true solution phase. The self-emulsifying nano-phase was characterized as spherical particles with an average diameter of approximately 100 nm. Pharmacodynamic assessments revealed that both Xiao-Chai-Hu decoction and its self-emulsifying nano-phase significantly reduced liver coefficients and alanine aminotransferase (ALT) levels compared to controls (P<0.05). However, no statistically significant differences were observed in regards to aspartate aminotransferase (AST) concentrations, malondialdehyde (MDA) content, or superoxide dismutase (SOD) activity between the treatment groups and control (P>0.05). These findings indicate that both Xiao-Chai-Hu decoction and its self-emulsifying nano-formulation ameliorated D-GalN-induced acute liver injury, albeit without statistically distinguishable efficacy between them (P>0.05). CONCLUSION: The presence of a self-emulsifying nano-phase within Xiao-Chai-Hu decoction is confirmed, and this nano-phase emerges as a therapeutically efficacious component in mitigating acute liver injury.

A novel nano-drug delivery system of glycyrrhetinic acid-mediated intracellular breakable brucine for enhanced anti-hepatitis B efficacy.

Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3'-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.

Preparation, characterization, and liver targeting evaluation of a novel sustained-release brucine self-assembled micelle mediated by glycyrrhetinic acid.

Background: Cancer is a serious threat to human life, health and social development. In recent years, nanomicelles, as an emerging drug carrier material, have gradually entered people's field of vision because of their advantages of improving bioavailability, maintaining drug levels, reducing systemic side effects and increasing drug accumulation at target sites. Methods: In this study, B-GPSG nano-micelles were prepared by film dispersion hydration method using brucine as model drug and glycyrrhetinic acid-polyethylene glycol-3-methylene glycol-dithiodipropionic acid-glycerol monostearate polymer as nano-carrier. The preparation process, characterization, drug release in vitro, pharmacokinetics and liver targeting were investigated. Results: The results showed that the range of particle size, polydispersion index and Zeta potential were 102.7 ± 1.09 nm, 0.201 ± 0.02 and -24.5 ± 0.19 mV respectively. The entrapment efficiency and drug loading were 83.79 ± 2.13% and 12.56 ± 0.09%, respectively. The drug release experiments in vitro and pharmacokinetic experiments showed that it had obvious sustained release effect. For pharmacokinetics study, it shows that both the B-GPSG solution group and the B-PSG solution group changed the metabolic kinetic parameters of brucine, but the B-GPSG solution group had a better effect. Compared with the B-PSG solution group, the drug was more prolonged in rats. The half-life in the body and the retention time in the body of B-GPSG are more helpful to improve the bioavailability of the drug and play a long-term effect. The tail vein injection results of mice indicate that B-GPSG can target and accumulate brucine in the liver without affecting other key organs. Cell uptake experiments and tissue distribution experiments in vivo show that glycyrrhetinic acid modified nano-micelles can increase the accumulation of brucine in hepatocytes, has a good liver targeting effect, and can be used as a new preparation for the treatment of liver cancer. Conclusion: The B-SPSG prepared in this experiment can provide a new treatment method and research idea for the treatment of liver cancer.

Five new sesquiterpenoids isolated from Dictamnus dasycarpus Turcz.

Five new sesquiterpenoids, dictamtrinorguaianols E and F (1-2), and dictameudesmnosides F, G, and H (3-5), along with seven known sesquiterpenoids (6-12) were isolated from Dictamnus dasycarpus Turcz. The structures of all new compounds were characterized by spectroscopic methods, including UV, IR, HR-ESI-MS, and 1D and 2D NMR. The In-vitro anti-proliferative activities of all the compounds against two human cancer cell lines (SW982 and A549) were evaluated by CCK-8 assay. Compounds 1 and 4 showed medium anti-proliferative activity against SW982 cells, with IC50 values of 3.49 ± 0.10 and 6.42 ± 1.23 µM, respectively. Additionally, compounds 2, 7, and 8 exhibited medium anti-proliferative activity against A549 cells, with IC50 values ranging from 0.80 ± 0.05 to 6.60 ± 0.46 µM.

[Application and advance of artificial antigens in studies on allergic reaction of traditional Chinese medicine injections].

There are some small molecules with potential allergenicity in traditional Chinese medicine injections. They are lack of immunogenicity due to their small molecular weight, but they can lead to allergic reactions when they were coupled with appropriate vectors. Therefore, how to couple small molecule semi-antigens with vectors to prepare complete antigens with immunogenicity and reactogenicity is the key for screening small molecular allergenic substances out of traditional Chinese medicine injections. In terms of semi-antigen characteristics of traditional Chinese medicine injections, vector selection and application, coupling method and complete antigen purification and identification, the author introduces the latest research situations of artificial antigen and antibody preparation technology, the advance in experimental studies on screening of allergenic substances in traditional Chinese medicine injections, as well as the application prospect of immuno-chip technology in studies on allergenic substances in traditional Chinese medicine injections, with the aim of providing new experimental thoughts and methods for safety control of traditional Chinese medicine injections.

Rhodiola rosea polysaccharides-based nanoparticles loaded with DOX boosts chemo-immunotherapy for triple-negative breast cancer by re-educating Tumor-associated macrophages.

Hydrophobic drug delivery vectors suffer significant challenges in cancer therapy, including efficient encapsulation and tumor targeting ability. In the present study, Rhodiola rosea polysaccharides (RHPs), which have the ability to modulate Tumor-associated macrophages and typical structural characteristics, were employed as an immunoactive vector for drug delivery. Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assembly and tumor-targeting behavior. Further, the hydrophobic drug, doxorubicin (DOX), was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Additionally, the optimally formed DOX@FA-RHPs-SA had a uniform size distribution of approximately 196 nm and a pH-sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that tumor cells could efficiently uptake DOX@FA-RHPs-SA. Furthermore, the modulatory function of the FA-RHPs-SA on RAW264.7 macrophages was also demonstrated in the transition from M0 to M1 phenotypes, and the M2 differentiated into the M1. Finally, the in vivo antitumor study revealed that the inhibitory effect of DOX@FA-RHPs-SA was superior to the DOX monotherapy treatment, and the new preparation functioned synergistically by inducing tumor cell apoptosis and modulating immune cell function. In conclusion, this study described an RHPs-based hydrophobic delivery vector and achieved an additional helpful antitumor effect by modulating Tumor-associated macrophages.

[Study on intestinal absorption kinetics of syringopicroside in rats].

OBJECTIVE: To study the intestinal absorption mechanism of traditional Chinese medicine monomer syringopicroside in rats. METHOD: The in situ rat single-pass intestinal perfusion model was established to detect the concentration of syringopicroside by HPLC. The absorption at different intestine segments in rat and the influence of concentration, pH and P-glycoprotein inhibitors of the drug solution on the absorption of syringopicroside were also observed. RESULT: The absorption rate constant (K,) of syringopicroside at duodenum, jejunum, ileum, and colon were 0.00255, 0.00630, 0.00900, 0.00799 min- , respectively; Ka from intestine at syringopicroside concentration of 0.090, 0.180, 0.360 g x L(-1) were 0.00370, 0.00708, 0.00694 min(-1), respectively; and Ka at pH of 7.4, 6.8 and 5.0 were 0.00733, 0.00747, 0.00362 min(-1), respectively. P-glycoprotein inhibitor on the intestinal absorption of syringopicroside showed significant influence (P < 0.05). CONCLUSION: Syringopicroside is well absorbed at the lower small intestine. When the drug concentration is low, the absorption rate constant is low, where as Ka increases at medium and high concentrations; the Ka is low at pH 5.0 and increases at pH 6.8 and pH 7.4. Syringopicroside is proved to be a substrate of P-glycoprotein.

Research on the progress of Traditional Chinese medicine components and preparations on histone deacetylase inhibitors - Like effects in the course of disease treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: During the treatment of diseases, histone deacetylases (HDAC) may have side effects such as strong immune inhibition and drug resistance, which may lead to damage of heart, liver and kidney. Traditional Chinese medicine (TCM) is a valuable and unique resource in China, which has good efficacy and safety. At present, it has been found that Chinese herbal compounds and active ingredients can effectively inhibit the expression of HDAC. Moreover, pharmacological studies have shown that these TCMs have shown therapeutic effects in the treatment of cancer, cardiovascular and cerebrovascular diseases, orthopedic diseases and skin diseases. AIM OF THE REVIEW: This article reviews the mechanism of action of HDAC, and introduces the epigenetic correlation between TCM and HDAC. We expounded the histone deacetylase inhibitor (HDACi)-like inhibitory effect and clinical application of natural drugs, and summarized the research progress of TCM on HDAC in recent years. MATERIALS AND METHODS: We collected relevant information published before March 2022 by searching the literature in various online databases such as PubMed, CNKI, Wanfang Database, Elsevier, Web of Science and China Biomedical Database. Search terms include "HDAC" or "HDACi", as well as "herb" or "herbal ingredient". RESULTS: A large number of studies have proved that many TCMs and their chemical components have the effect of inhibiting HDAC activity, which is highly selective, acts on different HDAC subtypes, and plays a certain therapeutic effect in cancer, cardiovascular and cerebrovascular diseases, orthopedic diseases, skin diseases and other diseases by inhibiting the process of HDAC. DISCUSSION AND CONCLUSIONS: The review of this paper is helpful to understand and excavate the active components of TCM, further explore the role of plant drugs with HDACi-like effect in diseases, and provide ideas for the development of new HDACi.

A comprehensive review of the botany, ethnopharmacology, biochemistry, pharmacology, pharmacokinetics and toxicity of Filifolium sibiricum (L.)Kitam.

Filifolium sibiricum (L.)Kitam (F. sibiricum), a compositae plant, is especially used to inhibit drug-resistant bacteria in folk medicine. Modern pharmacological studies also confirmed a variety of pharmacological properties about sedative activities, antibacterial activity, anti-inflammatory activity, analgesic activities, antitussive and asthma relieving. In this paper, the research progress of F. sibiricum in botany, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology was reviewed. Prospects for future investigation and application of this herb were also discussed. Information on F. sibiricum was gathered from various sources, including books on traditional Chinese herbal medicine and scientific databases such as PubMed, Google Scholar, Science Direct, Baidu Scholar, CNKI and other professional websites. The results indicate that ~ 66 chemical compounds were isolated and identified from F. sibiricum. Among them, flavonoids are generally considered to be the main bioactive and characteristic ingredients. F. sibiricum is a traditional Chinese medicine with pharmacological activities such as the immune system, nervous system, respiratory system and cardiovascular and cerebrovascular systems. Most importantly, we should concentrate on developing new drugs related to F. sibiricum, so as to exert greater potential for treatment.

A novel polymer micelle as a targeted drug delivery system for 10-hydroxycamptothecin with high drug-loading properties and anti-tumor efficacy.

A novel polyethylene glycol-polycaprolactone-poly-l-tyrosine (MPEG-PCL-PTyr) amphiphilic triblock copolymer micelle was synthesized for the first time. 10-hydroxycamptothecin (HCPT) was embedded in MPEG-PCL-PTyr nanomicelles using the emulsion solvent evaporation method. A series of was conducted to confirm the structure of the compound and to evaluate the physical properties of the MPEG-PCL-PTyr nanomicelles. Cellular uptake, cytotoxicity, and apoptosis were assessed using flow cytometry and MTT assays. Confocal microscopy and flow cytometry results demonstrated that the nanocapsules carrying HCPT had significantly increased anti-tumor activity against HepG2 cells and could target HepG2 cell lysosomes with obvious liver targeting. In addition, the drug-loaded nanomicelles could significantly block the S phase of cancer cells and induce apoptosis; thus, they could be potential carriers for future 10-HCPT delivery and cancer treatment.

Investigation of the antidepressant mechanism of combined Radix Bupleuri and Radix Paeoniae Alba treatment using proteomics analysis of liver tissue.

Depression is a chronic, common mental illness characterized by depressed mood, anxiety, insomnia, cognitive impairment, and even suicidal tendency. In traditional Chinese medicine theory, the cause of depression is deemed to be "stagnation of liver qi". So relieving "stagnation of liver qi" is effective for depression. The combination of Radix Bupleuri and Radix Paeoniae Alba, which is used to soothe the liver and relieve depression, has antidepressant effects, but the mechanisms of the effects are still unclear. In this study, a rat model of chronic unpredictable mild stress was established as a model of depression, and proteomics analysis was used to explore the potential mechanisms of this combination in alleviating depression. Biological information analysis was performed on the selected differential proteins, and the enriched pathways mainly included the Jak-STAT signaling pathway, valine, leucine, and isoleucine degradation, and oxidative phosphorylation. The expression of key proteins included metallothionein-1, cyclin-dependent kinase, ubiquitin carboxyl-terminal hydrolase-1, and Cryab was further verified by western blotting, and the results which were consistent with the proteomics results, confirmed the reliability of the proteomic analysis. The antidepressant mechanism of combined Radix Bupleuri and Radix Paeoniae Alba treatment may be related to the oxidative stress response, neuroplasticity, the immune response, and neuroprotection.

Tumor-targeted hyaluronic acid-mPEG modified nanostructured lipid carriers for cantharidin delivery: An in vivo and in vitro study.

AIM: Cantharidin (CTD), the major component of the anti-cancer medicine obtained from Mylabris cichorii, exerts good inhibitory effects on several cancers, such as liver and breast cancer. However, owing to its toxicity, its oral administration can cause various adverse effects, limiting its clinical applications. Therefore, the development of a novel nano-drug delivery system for CTD would be highly beneficial. METHODS: A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH2); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm. RESULTS: Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo. Fluorescence in vivo endo-microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%. CONCLUSIONS: Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy.

Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer.

BACKGROUND: Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. This compound can reduce tumors and improve immune function. However, the side effects of NCTD have limited its application. There is a marked need to reduce the side effects and increase the efficacy of NCTD. AIM: To develop a nanomaterial carrier, NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel), aiming to improve the anticancer activity of NCTD and reduce the drug dose. METHODS: NCTD-IRMOF-3-Gel was obtained by a coordination reaction. The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated. Cell cytotoxicity assays, flow cytometry, and apoptosis experiments in mouse hepatoma (Hepa1-6) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models. RESULTS: The particle size of NCTD-IRMOF-3-Gel was 50-100 nm, and the particle size distribution was uniform. The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect. The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation, and the inhibition rate increased with increasing drug concentration. By flow cytometry, NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases, and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest. Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells. CONCLUSION: Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.