Research progress in the ethnopharmacology, phytochemistry, pharmacology, toxicology, and quality control of Valeriana jatamansi Jones.

ETHNOPHARMACOLOGIC RELEVANCE: Valeriana jatamansi Jones, belongs to the Valerianaceae family, is widely used in traditional Chinese medicine (TCM) and Ayurveda, traditional Indian medicine (TIM). This traditional herb has been officially listed in the pharmacopoeia of sixteen countries. Its usage was first described in Diannan Bencao, also known as "Zhizhuxiang", is a famous folk medicine herb with a long history of medicinal usage in China, and it was used to treat indigestion, flu, and mental disorders in the Han, Achang, Bai, Blang, Dai, Jingpo, Naxi, and Wa ethnic groups. In recent years, V. jatamansi has attracted worldwide attention as an important medicinal due to its pharmacological activity especially in nervous and digestive systems, and multiple uses. AIM OF THE STUDY: The current review aims to provide a comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity, and quality control of V. jatamansi. MATERIALS AND METHODS: The relevant information of V. jatamansi was obtained from several databases including Web of Science, PubMed, ACS Publications, Google Scholar, Baidu Scholar, CNKI, Ph.D. and MSc dissertations, using "Valeriana jatamansi Jones", "Valeriana jatamansi", and "" as keywords. After eliminating repetitive and low-quality reports, the remaining reports were analyzed and summarized to prepare this review. Plant information was retrieved by www.worldfloraonline.org and www.gbif.org using "Valeriana jatamansi Jones" as keyword. RESULTS: V. jatamansi has been historically utilized as a traditional medicine to treat various diseases, including infectious, inflammatory, neurological, and gastrointestinal disorders. More than 400 compounds have been identified in V. jatamansi including iridoids, volatile oils, lignans, flavonoids, phenolic acids, phenylpropanoids, sesquiterpenes, sesquiterpene hydrocarbons, triterpenes as well as other compounds. The plant extracts and compounds showed various pharmacological activities such as antitumor, cytotoxic, antivirus, etc. In addition, V. jatamansi has found various applications in the agricultural, food, and cosmetics industry. CONCLUSION: A review of literature shows V. jatamansi has pharmacological properties valuable in treating diseases, particularly for antianxiety and gastrointestinal disorders. Despite a wide spectrum of effects from specific compounds, research mainly focuses on in vitro and in vivo, with a lack of pharmacokinetics, clinical trials and underlying mechanisms. Consequently, it becomes important to embark on additional researchs to elucidate the pharmacokinetics, material basis and mechanisms of V. jatamansi, thereby realizing the aspiration of its comprehensive utilization and sustainable development.

Modified Amber Particles as a Stabilizer to Construct Oil-in-Water Pickering Emulsions for Improved Thermal Stability of Acorus tatarinowii Essential Oil.

Lingzhu Pulvis is a classic formulation for treating febrile convulsions in children. However, Acorus tatarinowii essential oil (AT-EO) in this prescription is prone to volatilization and oxidation, compromising the efficacy and quality control of this formulation. Herein, based on the concept of "combination of medicine and adjuvant", Pickering emulsion technology was applied to enhance the stability of AT-EO using modified amber as a stabilizer. Amber was a resinous medicinal powder in Lingzhu Pulvis and was modified into a suitable stabilizer for Pickering emulsion through surface modification. A thermal stability study indicated that Pickering emulsion, stabilized by modified amber, exhibited a higher retention rate of AT-EO and lower levels of peroxide value and malondialdehyde content compared to those of the pure AT-EO group after heat treatment at 40 °C for 1, 3, and 8 h. Additionally, component analysis in content and composition revealed that the volatile components of AT-EO in the Pickering emulsion were more stable during the thermal treatment process. This study convincingly illustrates the potential of a Pickering emulsion stabilized with modified medicinal powders to improve the thermal stability of the essential oil.

Deciphering the antidepressant effects of Rosa damascena essential oil mediated through the serotonergic synapse signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa damascena is an ancient plant with significance in both medicine and perfumery that have a variety of therapeutic properties, including antidepressant, anti-anxiety, and anti-stress effects. Rose damascena essential oil (REO) has been used to treat depression, anxiety and other neurological related disorders in Iranian traditional medicine. However, its precise mechanism of action remains elusive. AIM OF THE STUDY: The aim of this study was to investigate the impact and mechanism underlying the influence of REO on chronic unpredictable mild stress (CUMS) rats. MATERIALS AND METHODS: Gas chromatography-mass spectrometry (GC-MS) technique coupling was used to analyze of the components of REO. A CUMS rat model was replicated to assess the antidepressant effects of varying doses of REO. This assessment encompassed behavioral evaluations, biochemical index measurements, and hematoxylin-eosin staining. For a comprehensive analysis of hippocampal tissues, we employed transcriptomics and incorporated weighting coefficients by means of network pharmacology. These measures allowed us to explore differentially expressed genes and biofunctional pathways affected by REO in the context of depression treatment. Furthermore, GC-MS metabolomics was employed to assess metabolic profiles, while a joint analysis in Metscape facilitated the construction of a network elucidating the links between differentially expressed genes and metabolites, thereby elucidating potential relationships and clarifying key pathways regulated by REO. Finally, the expression of relevant proteins in the key pathways was determined through immunohistochemistry and Western blot analysis. Molecular docking was utilized to investigate the interactions between active components and key targets, thereby validating the experimental results. RESULTS: REO alleviated depressive-like behavior, significantly elevated levels of the neurotransmitter 5-hydroxytryptamine (5-HT), and reduced hippocampal neuronal damage in CUMS rats. This therapeutic effect may be associated with the modulation of the serotonergic synapse signaling pathway. Furthermore, REO rectified metabolic disturbances, primarily through the regulation of amino acid metabolic pathways. Joint analysis revealed five differentially expressed genes (EEF1A1, LOC729197, ATP8A2, NDST4, and GAD2), suggesting their potential in alleviating depressive symptoms by modulating the serotonergic synapse signaling pathway and tryptophan metabolism. REO also modulated the 5-HT2A-mediated extracellular regulated protein kinases-cAMP-response element binding protein-brain-derived neurotrophic factor (ERK-CREB-BDNF) pathway. In addition, molecular docking results indicated that citronellol, geraniol and (E,E)-farnesol in REO may serve as key active ingredients responsible for its antidepressant effects. CONCLUSIONS: This study is the first to report that REO can effectively alleviate CUMS-induced depression-like effects in rats. Additionally, the study offers a comprehensive understanding of its intricate antidepressant mechanism from a multi-omics and multi-level perspective. Our findings hold promise for the clinical application and further development of this essential oil.

Preparation technologies, structural features, and biological activities of polysaccharides from Mesona chinensis Benth.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Mesona chinensis Benth. (or Platostoma palustre (Blume) A. J. Paton) is an important medicinal and edible plant also known as the Hsian-tsao in China and Southeast Asian countries. It is cold in nature and sweet in taste, with the effects of clearing heat, relieving heatstroke and diuretic, and traditionally used to treat heatstroke, erysipelas, hypertension, joint pain and other diseases in folk medicine. It is also a popular supplement with the function of detoxifying and heat-clearing use in Asia. It is used to be processed into the popular tea, Bean jelly, and so on. Published studies have demonstrated that polysaccharides from M. chinensis (MCPs) are one of the principal bioactive ingredients with a variety of health-promoting effects in the prevention and treatment of diseases, including antioxidant, immunomodulation, anti-inflammatory, hepatoprotective, anti-tumor, hypoglycemic, regulation of gut microbiota, and other pharmacological properties. AIM OF THE REVIEW: This review aims to compile the extraction and purification methods, structural characteristics, pharmacological activities including the mechanism of action of MCPs, and to further understand the applications of M. chinensis in order to lay the foundation for the development of MCPs. MATERIALS AND METHODS: By inputting the search term "Mesona chinensis polysaccharides", relevant research information was obtained from databases such as PubMed, Google Scholar, Web of Science, and China National Knowledge Infrastructure (CNKI). RESULTS: More than 40 polysaccharides have been extracted from M. chinensis, different extraction and purification methods have been described, as well as the structural features and pharmacological activities of MCPs have been systematically reviewed. Polysaccharides, as important components of M. chinensis, were mainly extracted by methods such as hot water dipping method, hot alkali extraction method, enzyme-assisted extraction method and ultrasonic-assisted extraction method, subsequently obtained by decolorization, deproteinization, removal of other small molecules and separation on various chromatographic columns. The chemical composition and structure of MCPs show diversity and have a variety of pharmacological activities, including antioxidant, immunomodulation, anti-inflammatory, hepatoprotective, anti-tumor, hypoglycemic, regulation of gut microbiota, and so on. CONCLUSIONS: This article systematically reviews the research progress of MCPs in terms of extraction and purification, structural characteristics, rheological gel properties, pharmacological properties, and safety assessment. The potentials and roles of M. chinensis in the field of medicine, functional food, and materials are further highlighted to provide references and bases for the high-value processing and utilization of MCPs.

Design, synthesis and bioactivity evaluation of the combination of evodiamine and erlotinib linked by indolequinone.

Compared with single-targeted therapy, the design and synthesis of heterozygous molecules is still a significant challenge for the discovery of antitumor drugs. Quinone oxidoreductase-1 (NQO1) is a potential target for selective cancer therapy due to its overexpression in many cancer cells and its unique bioredox properties. Based on the principle of combinatorial drug design, we successfully synthesized a new hybrid molecules 13 with an indolequinone structure. We found that the synthesized compounds exhibited much higher cytotoxicity against the tested cancer cells than free drugs. Further mechanism studies confirmed that compound 13 induced cell apoptosis was achieved by regulating p53-dependent mitochondrial pathway and cell cycle arrest at the G0/G1 phase.

Recent advances in Platycodon grandiflorum polysaccharides: Preparation techniques, structural features, and bioactivities.

Platycodon grandiflorum, a globally recognized medicinal and edible plant, possesses significant nutritional value and pharmacological value. In traditional Chinese medicine, it has the effects of tonifying the spleen and replenishing the Qi, moistening the lung and relieving the cough, clearing the heat and detoxifying, and relieving the pain. Accumulating evidence has revealed that the polysaccharides from P. grandiflorum (PGPs) are one of the major and representative biologically active macromolecules and have diverse biological activities, such as immunomodulatory activity, anti-inflammatory activity, anti-tumor activity, regulation of the gut microbiota, anti-oxidant activity, anti-apoptosis activity, anti-angiogenesis activity, hypoglycemic activity, anti-microbial activity, and so on. Although the polysaccharides extracted from P. grandiflorum have been extensively studied for the extraction and purification methods, structural characteristics, and pharmacological activities, the knowledge of their structures and bioactivity relationship, toxicologic effects, and pharmacokinetic profile is limited. The main purpose of the present review is to provide comprehensively and systematically reorganized information on extraction and purification, structure characterizations, and biological functions as well as toxicities of PGPs to support their therapeutic potentials and sanitarian functions. New valuable insights for future research regarding PGPs were also proposed in the fields of therapeutic agents and functional foods.

Extraction, purification, structural features, biological activities, modifications, and applications from Taraxacum mongolicum polysaccharides: A review.

Dandelion (Taraxacum mongolicum Hand.-Mazz), as a famous medicinal and edible plant, has the effects of clearing heat and detoxifying, diuresis, and resolving masses. Phytochemistry investigations revealed that T. mongolicum has various bioactive ingredients, mainly including flavonoids, sterols, polysaccharides, phenolic acids and volatile oils. There is growing evidence have shown that the polysaccharides from T. mongolicum (TMPs) are a class of representative pharmacologically bioactive macromolecules with a variety of biological activities both in vitro and in vivo, such as immunomodulatory, anti-inflammatory, anti-oxidant, anti-tumor, hepatoprotective, hypolipidemic and hypoglycemic, anti-bacterial, regulation of intestinal microbial, and anti-fatigue activities, etc. Additionally, the structural modification and potential applications of TMPs were also outlined. The present review aims to comprehensively and systematically collate the recent research progress on extraction and purification methods, structural characteristics, biological activities, mechanism of action, structural modification, and potential industry applications of TMPs to support their therapeutic potential and health care functions. Overall, the present review provides a theoretical overview for further development and utilization of TMPs in the fields of pharmaceutical and health food.

Basis with RNA-Seq and WGCNA to explore the effect of Frankincense essential oil on dextran sodium sulfate-induced ulcerative colitis through MAPK/NF-κB signaling.

PURPOSE: Frankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives. METHODS: The FREO components were analyzed by GC-MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, "quantity-effect" weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay. The expression of MAPK and NF-κB-related proteins by the Western Blotting and immunohistochemistry method. RESULTS: Treatment with FREO significantly improved the symptoms of weight loss, diarrhea, stool blood, and colon shortening in UC mice. Reduced intestinal mucosal damage and the degree of inflammatory cell infiltration in the colon. Decreased TNF-α and IL-6 levels in mice's serum and inhibited phosphorylation of ERK, p65 in MAPK and NF-κB signaling. CONCLUSION: FREO may decrease the inflammatory response to reduce the symptoms of UC by modulating the MAPK/ NF-κB pathway. This may be due to the synergistic interaction of the effective ingredient Hepten-2-yl tiglate, 6-methyl-5-, Isoneocembrene A and P-Cymene. This study provides a promising drug candidate and a new concept for the treatment of UC.

The JAK/STAT/NF-κB signaling pathway can be regulated by rosemary essential oil, thereby providing a potential treatment for DNCB-induced in mice.

OBJECTIVE: The purpose of this study was to investigate the mechanism through which rosemary essential oil treats atopic dermatitis. METHODS: A dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model was established and treated with low (1%), medium (2%), and high (4%) doses of Rosmarinus officinalis essential oil (EORO). Serum levels of interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) in each group were determined using enzyme-linked immunosorbent assay (ELISA). Skin tissues were stained with hematoxylin-eosin and toluidine blue. We used network pharmacology and molecular docking techniques to verify the biological activity of essential proteins and their corresponding compounds in the pathway. Gas chromatography-mass spectrometry (GC-MS) was used for metabolomics analysis and multivariate statistical analysis of mouse serum to screen differential metabolites and metabolic pathway analysis. Protein expression of p-JAK1, CD4+ cells, and IL-4 in the skin tissue was detected by immunohistochemistry analysis. Protein levels of STAT3, p-STAT3, P65, and p-P65 in damaged skin tissues were detected using western blotting. RESULT: The skin of mice in the model group showed different degrees of erythema, dryness, scratches, epidermal erosion and shedding, and crusting. After treatment, the serum levels of IL-6 and TNF-α in EORO group were significantly decreased, and the expression of p-JAK1,CD4 + cells, IL-4, p-P65 / P65 and p-STAT3 / STAT3 proteins in skin tissues were decreased. CONCLUSION: EORO can effectively improve DNCB-induced AD-like skin lesions in mice by regulating the JAK/STAT/NF-κB signaling pathway, thereby reducing the production of downstream arachidonic acid metabolites, inhibiting skin inflammation, and restoring epidermal barrier function.

Development of curcumin-loaded galactosylated chitosan-coated nanoparticles for targeted delivery of hepatocellular carcinoma.

Curcumin (CUR) has good antitumor effects, but its poor aqueous solubility severely limits its clinical application and the systemic nonspecific distribution of the free drug in tumor patients is a key therapeutic challenge. In order to overcome the limitations of free drugs and improve the therapeutic efficacy, we developed novel galactosylated chitosan (GC)-modified nanoparticles (GC@NPs) based on poly (ethylene glycol) methyl ether-block-poly (lactide-co-glycolide) (PEG-PLGA), which can target asialoglycoprotein receptor (ASGPR) expressed on hepatocellular carcinoma cells and have excellent biocompatibility. The results showed that the drug loading (DL) of CUR was approximately 4.56 %. A favorable biosafety profile was maintained up to concentrations of 500 µg/mL. Furthermore, in vitro cellular assays showed that GC@NPs could be efficiently internalized by HepG2 cells via ASGPR-mediated endocytosis and successfully released CUR for chemotherapy. More importantly, in vivo anti-tumor experiments revealed that GC@NPs were able to accumulate effectively within tumor sites through EPR effect and ASGPR-mediated endocytosis, leading to superior inhibition of tumor growth compared to free CUR. Overall, GC@NPs are a promising CUR nanocarrier for enhanced tumor therapy with a good biosafety profile.

Phloretin Transfersomes for Transdermal Delivery: Design, Optimization, and In Vivo Evaluation.

BACKGROUND: Phloretin (Phl) is a flavonoid compound that contains multiple phenolic hydroxyl groups. It is found in many plants, such as apple leaves, lychee pericarp, and begonia, and has various biological activities, such as antioxidant and anticancer effects. The strong hydrogen bonding between Phl molecules results in poor water solubility and low bioavailability, and thus the scope of the clinical application of Phl is limited. Therefore, it is particularly important to improve the water solubility of Phl for its use to further combat or alleviate skin aging and oxidative damage and develop antioxidant products for the skin. The purpose of this study was to develop and evaluate a phloretin transfersome gel (PTG) preparation for transdermal drug delivery to improve the bioavailability of the drug and delay aging. METHODS: Phloretin transfersomes (Phl-TFs) were prepared and optimized by the thin-film dispersion-ultrasonication method. Phl-TFs were characterized by transmission electron microscopy (TEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD). The Log P method was used to determine the solubility of the Phl-TFs. The skin penetration ability of the prepared PTG was evaluated using the Franz diffusion cell method. In addition, the in vivo pharmacokinetics of PTG were studied in rats, and an antioxidant activity investigation was conducted using a D-gal rat model. RESULTS: Phl-TFs were successfully prepared with a Soybean Phosphatidylcholine (SPC)/CHOL ratio of 2.7:1 w/v, a phloretin concentration of 1.3 mg/mL, a hydration time of 46 min, an ultrasound time of 5 min, and an ultrasound power of 180 W. The Log P was 2.26, which was significantly higher than that of phloretin (p < 0.05, paired t test). The results of the in vitro penetration test demonstrated that the cumulative skin penetration of the Phl-TFs after 24 h was 842.73 ± 20.86 µg/cm2. The data from an in vivo pharmacokinetic study showed that the Cmax and AUC of PTG were 1.39- and 1.97-fold higher than those of the phloretin solution gel (PSG), respectively (p < 0.05, paired t test). The experimental results in aging rats showed that PTG had a better antioxidant effect. CONCLUSIONS: Phl-TFs and PTG preparations with a good shape, safety, and stability were successfully prepared. In vivo pharmacokinetics and preliminary antioxidant experiments further verified the transdermal penetration and antioxidant activity of the phloretin transdermal drug delivery preparation, providing an experimental basis for its further development.

Targeted Drug Delivery Systems for Curcumin in Breast Cancer Therapy.

Breast cancer (BC) is the most prevalent type of cancer in the world and the main reason women die from cancer. Due to the significant side effects of conventional treatments such as chemotherapy and radiotherapy, the search for supplemental and alternative natural drugs with lower toxicity and side effects is of interest to researchers. Curcumin (CUR) is a natural polyphenol extracted from turmeric. Numerous studies have demonstrated that CUR is an effective anticancer drug that works by modifying different intracellular signaling pathways. CUR's therapeutic utility is severely constrained by its short half-life in vivo, low water solubility, poor stability, quick metabolism, low oral bioavailability, and potential for gastrointestinal discomfort with high oral doses. One of the most practical solutions to the aforementioned issues is the development of targeted drug delivery systems (TDDSs) based on nanomaterials. To improve drug targeting and efficacy and to serve as a reference for the development and use of CUR TDDSs in the clinical setting, this review describes the physicochemical properties and bioavailability of CUR and its mechanism of action on BC, with emphasis on recent studies on TDDSs for BC in combination with CUR, including passive TDDSs, active TDDSs and physicochemical TDDSs.

Review targeted drug delivery systems for norcantharidin in cancer therapy.

Norcantharidin (NCTD) is a demethylated derivative of cantharidin (CTD), the main anticancer active ingredient isolated from traditional Chinese medicine Mylabris. NCTD has been approved by the State Food and Drug Administration for the treatment of various solid tumors, especially liver cancer. Although NCTD greatly reduces the toxicity of CTD, there is still a certain degree of urinary toxicity and organ toxicity, and the poor solubility, short half-life, fast metabolism, as well as high venous irritation and weak tumor targeting ability limit its widespread application in the clinic. To reduce its toxicity and improve its efficacy, design of targeted drug delivery systems based on biomaterials and nanomaterials is one of the most feasible strategies. Therefore, this review focused on the studies of targeted drug delivery systems combined with NCTD in recent years, including passive and active targeted drug delivery systems, and physicochemical targeted drug delivery systems for improving drug bioavailability and enhancing its efficacy, as well as increasing drug targeting ability and reducing its adverse effects.

Development of Paeonol Liposomes: Design, Optimization, in vitro and in vivo Evaluation.

Background: Ulcerative colitis (UC) is one of the intractable diseases recognized by the World Health Organization, and paeonol has been proven to have therapeutic effects. However, the low solubility of paeonol limits its clinical application. To prepare and optimize paeonol liposome, study its absorption mechanism and the anti-inflammatory activity in vitro and in vivo, in order to provide experimental basis for the further development of paeonol into an anti-inflammatory drug in the future. Methods: Paeonol loaded liposomes were prepared and optimized by thin film dispersion-ultrasonic method. The absorption mechanism of paeonol-loaded liposomes was studied by pharmacokinetics, in situ single-pass intestinal perfusion and Caco-2 cell monolayer model, the anti-inflammatory activity was studied in a mouse ulcerative model. Results: Box-Behnken response surface methodology permits to screen the best formulations. The structural and morphological characterization showed that paeonol was entrapped inside the bilayer in liposomes. Pharmacokinetic studies found that the AUC0-t of Pae-Lips was 2.78 times than that of paeonol suspension, indicating that Pae-Lips significantly improved the absorption of paeonol. In situ single intestinal perfusion and Caco-2 monolayer cell model results showed that paeonol was passively transported and absorbed, and was the substrate of P-gp, MRP2 and BCRP, and the Papp value of Pae-Lips was significantly higher than that of paeonol. In vitro and in vivo anti-inflammatory experiments showed that compared with paeonol, Pae-Lips exhibited excellent anti-inflammatory activity. Conclusion: In this study, Pae-Lips were successfully prepared to improve the oral absorption of paeonol. Absorption may involve passive diffusion and efflux transporters. Moreover, Pae-Lips have excellent anti-inflammatory activity in vitro and in vivo, which preliminarily clarifies the feasibility of further development of Pae-Lips into oral anti-inflammatory drugs.

Valerian essential oil for treating insomnia via the serotonergic synapse pathway.

Valerian volatile oil can be used in the treatment of insomnia; however, the active components and mechanisms of action are currently unclear. Therefore, we used transcriptome sequencing and weight coefficient network pharmacology to predict the effective components and mechanism of action of valerian volatile oil in an insomnia model induced by intraperitoneal injection of para-Chlorophenylalanine (PCPA) in SD rats. Valerian essential oil was given orally for treatment and the contents of 5-hydroxytryptamine receptor 1 A (5-HT1AR), γ-aminobutyric acid (GABA), cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) in the hippocampus of rats in each group were detected by enzyme-linked immunosorbent assay (ELISA), western blot, Polymerase Chain Reaction (PCR), and immunohistochemistry. The results showed that after treatment with valerian essential oil, insomnia rats showed significantly prolonged sleep duration and alleviated insomnia-induced tension and anxiety. Regarding the mechanism of action, we believe that caryophyllene in valerian essential oil upregulates the 5-HT1AR receptor to improve the activity or affinity of the central transmitter 5-HT, increase the release of 5-HT, couple 5-HT with a G protein coupled receptor, convert adenosine triphosphate (ATP) into cAMP (catalyzed by ADCY5), and then directly regulate the downstream pathway. Following pathway activation, we propose that the core gene protein kinase PKA activates the serotonergic synapse signal pathway to increase the expression of 5-HT and GABA, thus improving insomnia symptoms and alleviating anxiety. This study provides a theoretical basis for the application of valerian volatile oil in health food.

Investigation and experimental validation of curcumin-related mechanisms against hepatocellular carcinoma based on network pharmacology.

OBJECTIVES: To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation. METHODS: The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)|-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-|α (PFT-|α) and GSK690693 for further investigation. RESULTS: The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-|α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated. CONCLUSIONS: Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.

Urokinase-type plasminogen activator receptor (uPAR) as a therapeutic target in cancer.

Urokinase-type plasminogen activator receptor (uPAR) is an attractive target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is closely related to the invasion and metastasis of malignant tumours, plays important roles in the degradation of extracellular matrix (ECM), tumour angiogenesis, cell proliferation and apoptosis, and is associated with the multidrug resistance (MDR) of tumour cells, which has important guiding significance for the judgement of tumor malignancy and prognosis. Several uPAR-targeted antitumour therapeutic agents have been developed to suppress tumour growth, metastatic processes and drug resistance. Here, we review the recent advances in the development of uPAR-targeted antitumor therapeutic strategies, including nanoplatforms carrying therapeutic agents, photodynamic therapy (PDT)/photothermal therapy (PTT) platforms, oncolytic virotherapy, gene therapy technologies, monoclonal antibody therapy and tumour immunotherapy, to promote the translation of these therapeutic agents to clinical applications.

The influence of rhein on the absorption of rehmaionoside D: In vivo, in situ, in vitro, and in silico studies.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese Medicine, Rehmannia glutinosa (Gaertn.) DC., as the principle herb of ShengDiHuang Decotion (SDHD), has the effect of cooling blood and hemostasis, and tonifying the yin and kidney. Rheum L., as adjuvant herbs, assist Rehmannia glutinosa (Gaertn.) DC. to promote blood circulation to remove blood stasis. AIM OF STUDY: To study the mechanism of Rhein (RH) involved in the promotion of Rehmannioside D (RD) absorption by pharmacokinetic studies, single-pass intestinal perfusion, Caco-2 cell models, molecular docking technique and western blotting. MATERIALS AND METHODS: Initially, the intestinal absorption of RD in the presence or absence of RH was conducted through pharmacokinetic studies. Thereafter, the intestinal absorption of RD and RH was studied using the single-pass intestinal perfusion and Caco-2 cell models. Finally, using molecular docking technique and western blotting. RESULTS: We found that the promotion of RD absorption by RH was mediated by breast cancer resistance and multidrug resistance-associated protein 2, thereby affecting the permeability of the intestinal epithelium. Additionally, RH and RD can competitively bind to breast cancer resistance and multidrug resistance-associated protein 2, and that RH inhibits the expression of breast cancer resistance and multidrug resistance-associated protein 2 in the ileum to promote the intestinal absorption of RD. CONCLUSION: This study reveals the mechanisms associated with the RH-mediated promotion of RD absorption and provides a basis for further exploring the synergistic effect of Rehmannia glutinosa (Gaertn.) DC and rhubarb.

The Mechanism Action of German Chamomile (Matricaria recutita L.) in the Treatment of Eczema: Based on Dose-Effect Weight Coefficient Network Pharmacology.

To determine the active ingredients in German chamomile volatile oil and the mechanism of action in the treatment of eczema, this study used two parameters (ingredient content and oil-water partition coefficient) and established a new network pharmacology method based on the dose-effect weight coefficient. Through the new network pharmacology method, we found that German chamomile volatile oil regulated T-cell lymphatic subpopulations to inhibit the Th17 cell differentiation signaling pathway. This resulted in a reduction of interleukin 17 (IL-17), thereby inhibiting the activation of the nuclear factor kappa beta (NF-κB) and MAPK pathways, decreasing the secretion of the pro-inflammatory factors (tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6)), and reducing inflammation. In this study, a new dose-effect relationship synergistic network pharmacology method was established to provide a new method for the screening of effective ingredients and pathways of drugs, and to provide a basis for the follow-up studies of German chamomile volatile oil in the treatment of eczema.

Antioxidant, Anti-Aging and Organ Protective Effects of Total Saponins from Aralia taibaiensis.

AIM: Aralia taibaiensis is a natural medicinal and food plant that is rich in triterpenoid saponins with hypoglycaemic, antioxidant, hepatoprotective, anti-gastric ulcer and anti-inflammatory effects. This study has significance in terms of the antioxidant, anti-aging and organ protective effects of Aralia taibaiensis total saponins (TSAT) in D-galactose-induced aging rats. METHODS: The saponin composition of TSAT was determined and quantified by high performance liquid chromatography (HPLC). We consolidated the antioxidant and enzyme inhibitory activities of TSAT in vitro and assessed the effects of TSAT on daily mobility, body weight, behaviour, organ indices, oxidation-related indices and pathological changes in aging rats. RESULTS: In vitro experiments showed that TSAT had a scavenging effect on 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), tyrosinase, hydroxyl radicals (HO•) and superoxide radicals (•O2-) and was closely related to the dose of TSAT. In vivo experiments showed that after 8 weeks of continuous gavage administration, the rats gradually recovered their body weight, daily activity ability, learning and memory ability and organ index and effectively improved D-gal-induced organ injury. Specifically, TSAT significantly increased the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) and significantly decreased malondialdehyde (MDA) levels in the serum, brain, heart, lung, spleen and kidney of aging rats compared to the model group. In addition, TSAT significantly inhibited the D-gal-induced upregulation of hepatic alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. The histopathological results showed that TSAT reversed D-gal-induced damage to the brain, heart, lung, kidney, liver and spleen to varying degrees. CONCLUSION: TSAT is a high-quality natural product with antioxidant and anti-aging properties that can alleviate D-gal-induced aging damage in rats.