Deferiprone-resveratrol hybrid attenuates iron accumulation, oxidative stress, and antioxidant defenses in iron-loaded human Huh7 hepatic cells.

Chronic liver diseases are complications of thalassemia with iron overload. Iron chelators are required to remove excessive iron, and antioxidants are supplemented to diminish harmful reactive oxygen species (ROS), purposing to ameliorate oxidative liver damage and dysfunctions. The deferiprone-resveratrol hybrid (DFP-RVT) is a synthetic iron chelator possessing anti-ß-amyloid peptide aggregation, anti-malarial activity, and hepatoprotection in plasmodium-infected mice. The study focuses on investigating the antioxidant, cytotoxicity, iron-chelating, anti-lipid peroxidation, and antioxidant defense properties of DFP-RVT in iron-loaded human hepatocellular carcinoma (Huh7) cells. In the findings, DFP-RVT dose dependently bound Fe(II) and Fe(III) and exerted stronger ABTS•- and DPPH•-scavenging (IC50 = 8.0 and 164 µM, respectively) and anti-RBC hemolytic activities (IC50 = 640 µM) than DFP but weaker than RVT (p < 0.01). DFP-RVT was neither toxic to Huh7 cells nor PBMCs. In addition, DFP-RVT diminished the level of redox-active iron (p < 0.01) and decreased the non-heme iron content (p < 0.01) in iron-loaded Huh7 cells effectively when compared without treatment in the order of DFP-RVT > RVT ∼ DFP treatments (50 µM each). Moreover, the compound decreased levels of hepatic ROS in a dose-dependent manner and the level of malondialdehyde, which was stronger than DFP but weaker than RVT. Furthermore, DFP-RVT restored the decrease in the GSH content and GPX and SOD activities (p < 0.01) in iron-loaded Huh7 cells in the dose-dependent manner, consistently in the order of RVT > DFP-RVT > DFP. Thus, the DFP-RVT hybrid possesses potent iron chelation, antioxidation, anti-lipid peroxidation, and antioxidant defense against oxidative liver damage under iron overload.

Hidden diversity and potential ecological function of phosphorus acquisition genes in widespread terrestrial bacteriophages.

Phosphorus (P) limitation of ecosystem processes is widespread in terrestrial habitats. While a few auxiliary metabolic genes (AMGs) in bacteriophages from aquatic habitats are reported to have the potential to enhance P-acquisition ability of their hosts, little is known about the diversity and potential ecological function of P-acquisition genes encoded by terrestrial bacteriophages. Here, we analyze 333 soil metagenomes from five terrestrial habitat types across China and identify 75 viral operational taxonomic units (vOTUs) that encode 105 P-acquisition AMGs. These AMGs span 17 distinct functional genes involved in four primary processes of microbial P-acquisition. Among them, over 60% (11/17) have not been reported previously. We experimentally verify in-vitro enzymatic activities of two pyrophosphatases and one alkaline phosphatase encoded by P-acquisition vOTUs. Thirty-six percent of the 75 P-acquisition vOTUs are detectable in a published global topsoil metagenome dataset. Further analyses reveal that, under certain circumstances, the identified P-acquisition AMGs have a greater influence on soil P availability and are more dominant in soil metatranscriptomes than their corresponding bacterial genes. Overall, our results reinforce the necessity of incorporating viral contributions into biogeochemical P cycling.

Online preconcentration and determination of five alkaloids in Yangxinshi tablet by large-volume sample stacking and micelle to solvent stacking in cyclodextrin-modified electrokinetic chromatography.

The two-step preconcentration technique consisting of large-volume sample stacking (LVSS) and micelle to solvent stacking (MSS) in cyclodextrin-modified electrokinetic chromatography (CDEKC) was developed for the analysis of five cationic alkaloids in complex Chinese herbal prescriptions. Relevant parameters affecting separation and stacking performance were optimized separately. Under the optimal LVSS-MSS-CDEKC conditions, less analysis time and organic solvent were required, and the enhancement factors of analytes ranged from 12 to 15 compared with the normal CDEKC separation mode. Further, all validation results demonstrated good applicability and multiple alkaloids (epiberberine, dehydrocorydaline, jatrorrhizine, coptisine and berberine) in Yangxinshi tablet (YXST) have been simultaneously determined. This approach presents powerful potential for the determination of multiple components in complex preparations of Chinese medicine.

Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of sophorae tonkinensis radix et rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

The phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity of Forsythiae Fructus: An updated systematic review.

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.

Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

A review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology of Abri Herba (Ji-Gu-Cao).

Abri Herba (AH, known as 'Ji-Gu-Cao' in China) has a long-term medicinal history of treating cholecystitis, acute and chronic hepatitis and non-alcoholic fatty liver (NAFL) in China or other Asian countries. This review aimed to provide a comprehensive analysis of AH in terms of ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and toxicology. The information involved in the study was collected from a variety of electronic resources, and >100 scientific studies have been used since 1962. Until now, 95 chemical compounds have been isolated and identified from AH and the seeds of Abrus cantoniensis Hance (ACH), including 47 terpenoids, 26 flavonoids and 4 alkaloids. The pharmacological activities of AH extracts and their pure compounds have been explored in the aspects of anti-hyperlipidaemia, hepatoprotection, anti-tumour, anti-viral, anti-bacterial, anti-inflammatory and analgesic, immunomodulation, antioxidant and others. The pharmacokinetics and excretion kinetics of AH in vivo and 15 traditional and clinical prescriptions containing AH have been sorted out, and the potential therapeutic mechanism and drug metabolism pattern were also summarised. The pods of ACH are toxic, with a median lethal dose (LD50) of 10.01 ± 2.90 g/kg (i.g.) in mice. Interestingly, the toxicity of ACH's pods and seeds decreased after boiling. However, the toxicity mechanism of pods of ACH is unclear, limiting its clinical application. Clinical trials in the future should be used to explore its safety. Meanwhile, as one of the relevant pharmacological activities, the effects and mechanism of AH on anti-hyperlipidaemia and hepatoprotection should be further studied, which is of great significance for understanding its mechanism of action in the treatment of NAFL disease and improving its clinical application.

Phenolic acids from Chicory roots ameliorate dextran sulfate sodium-induced colitis in mice by targeting TRP signaling pathways and the gut microbiota.

BACKGROUND: Inflammatory bowel disease (IBD) is a type of immune-mediated condition associated with intestinal homeostasis. Our preliminary studies disclosed that Cichorium intybus L., a traditional medicinal plant, also known as Chicory in Western countries, contained substantial phenolic acids displaying significant anti-inflammatory activities. We recognized the potential of harnessing Chicory for the treatment of IBD, prompting a need for in-depth investigation into the underlying mechanisms. METHODS: On the third day, mice were given 100, 200 mg/kg of total phenolic acids (PA) from Chicory and 200 mg/kg of sulfasalazine (SASP) via gavage, while dextran sodium sulfate (DSS) concentration was 2.5 % for one week. The study measured and evaluated various health markers including body weight, disease activity index (DAI), colon length, spleen index, histological score, serum concentrations of myeloperoxidase (MPO), nitric oxide (NO), superoxide dismutase (SOD), lipid oxidation (MDA), and inflammatory factors. We evaluated the TRP family and the NLRP3 inflammatory signaling pathways by Western blot, while 16S rDNA sequencing was used to track the effects of PA on gut microbes. RESULTS: It was shown that PA ameliorated the weight loss trend, attenuated inflammatory damage, regulated oxidative stress levels, and repaired the intestinal barrier in DSS mice. Analyses of Western blots demonstrated that PA suppressed what was expressed of transient receptor potential family TRPV4, TRPA1, and the expression of NLRP3 inflammatory signaling pathway, NLRP3 and GSDMD. In addition, PA exerted therapeutic effects on IBD by regulating gut microbiota richness and diversity. Meanwhile, the result of the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis showed that gut microbiota was mainly related to Membrane Transport, Replication and Repair, Carbohydrate Metabolism and Amino Acid Metabolism. CONCLUSION: PA derived from Chicory may have therapeutic effects on IBD by regulating the TRPV4/NLRP3 signaling pathway and gut microbiome. This study provides new insights into the effects of phenolic acids from Chicory on TRP ion channels and gut microbiota, revealing previously unexplored modes of action.

Combination of large-volume sample stacking with polarity switching and micelle electrokinetic chromatography for the analysis of anion compounds in Yangxinshi tablets.

INTRODUCTION: Yangxinshi tablet (YXST) is a traditional Chinese medicine preparation characterized by its high efficacy and safety for the treatment of cardiovascular diseases. Anionic compounds have been revealed as potential active components. However, there is currently limited research regarding its quality control. OBJECTIVE: We aimed to establish a strategy for the simultaneous separation and determination of five key anionic compounds in YXST. METHOD: A sensitive and efficient analytical method was developed and applied for the simultaneous separation and determination of five key compounds in YXST using large-volume sample stacking with polarity switching and micelle electrokinetic chromatography (LVSS-PS-MEKC) coupled with diode array detection. Crucial parameters, including sample volume, applied voltage, composition and pH of the running buffer, concentration of organic modifier, and switching time of the polarity, were systematically evaluated and optimized using a single variable method to enhance separation performance. Furthermore, the impact of cyclodextrin and sodium dodecyl sulfate as electrolyte modifiers was also investigated. RESULTS: Under the optimal conditions, baseline separation of the five compounds (daidzein, puerarin, glycyrrhiztinic acid, chlorogenic acid, and salvianolic acid B) was achieved within 20 min. In comparison to the conventional MEKC mode, the constructed LVSS-PS-MEKC method exhibited a more than sixfold increase in the enrichment factor. The method was validated in terms of linearity, precision, accuracy, 24 h stability, and recovery and successfully applied to analyze YXST samples. CONCLUSION: A sensitive strategy was developed for the simultaneous separation and determination of five key anionic components in YXST, offering a robust and efficient strategy for pharmaceutical analysis.

Structurally Diverse Coumarins from Peucedanum praeruptorum and their Anti-Inflammatory Activities via NF-κB Signaling Pathway.

The phytochemical study of Peucedanum praeruptorum led to the isolation of twenty-five coumarins (1-25). Of which, (±) praeruptol A (±1), one pair of previous undescribed seco-coumarin enantiomers were obtained. Their structures were established according to HR-ESI-MS, NMR, X-ray single crystal diffraction analysis, as well as ECD calculation. All compounds were tested for anti-inflammatory activity in the RAW264.7 macrophage model, and eight compounds (7-10, and 13-16) exhibited significant inhibitory effects with IC50 values ranging from 9.48 to 34.66 µM. Among them, compound 7 showed the strongest inhibitory effect, which significantly suppressed the production of IL-6, IL-1ß, and TNF-α, as well as iNOS and COX-2 in a concentration-dependent manner. Further investigated results showed that compound 7 exerted an anti-inflammatory effect via the NF-κB signaling pathway.

Anti-cancer effects of Coix seed extract through KCTD9-mediated ubiquitination of TOP2A in lung adenocarcinoma.

BACKGROUND: Coix seed extract (CSE), a traditional Chinese medicine, has been reported as an adjunctive therapy in cancers. However, the molecular targets are largely unclear. The study is designed to unveil its function in lung adenocarcinoma (LUAD) and the possible molecular mechanism. METHODS: The HERB database was utilized to predict the molecular targets of the Coix seed, followed by prognostic value prediction in the Kaplan-Meier Plotter database. LUAD cells were infected with sh-KCTD9 after co-culture with CSE, and cell viability, growth, proliferation, and apoptosis were determined. The substrates of KCTD9 were predicted using a protein-protein interaction network and verified. The expression of PD-L1, the contents of TNF-α, IFN-γ, CXCL10, and CXCL9 in the co-culture system of LUAD cells and T cells and the proliferation of T cells were evaluated to study the immune escape of LUAD cells in response to CSE and sh-KCTD9. Lastly, tumor growth and immune escape were observed in tumor-bearing mice. RESULTS: CSE inhibited malignant behavior and immune escape of LUAD cells, and the reduction of KCTD9 reversed the inhibitory effect of CSE on malignant behavior and immune escape of LUAD cells. Knockdown of KCTD9 expression inhibited ubiquitination modification of TOP2A, and knockdown of TOP2A suppressed immune escape of LUAD cells in the presence of knockdown of KCTD9. CSE exerted anticancer effects in mice, but the reduction of KCTD9 partially compromised the anticancer effect of CSE. CONCLUSION: CSE inhibits immune escape and malignant progression of LUAD through KCTD9-mediated ubiquitination modification of TOP2A.

Comparative study on curative effect and recurrence rate of chronic scapulohumeral periarthritis treated with different acupuncture techniques. / ä¸åŒé’ˆæ³•æ²»ç–—æ ¢æ€§è‚©å ³èŠ‚å‘¨å›´ç‚Žçš„ç–—æ•ˆåŠå¤å‘çŽ‡çš„å¯¹æ¯”ç ”ç©¶.

OBJECTIVES: To observe the effects of the local stimulation with 3 acupuncture techniques, i.e. Canggui Tanxue (needle insertion method like dark tortoise detecting point) technique, electroacupuncture (EA) and warm needling (WN) with filiform needles on shoulder pain, shoulder joint function, quality of life, inflammatory indicators and recurrence rate in the patients with chronic scapulohumeral periarthritis (CSP), so as to explore the optimal needling method of acupuncture for the predominant symptoms of CSP during the attack stage in the patients. METHODS: A total of 108 patients with CSP were randomly divided into a manual acupuncture (MA) group (36 cases, one case dropped off), a WN group (36 cases, 3 cases dropped off) and an EA group (36 cases, 1 case dropped off). In the three groups, Jianqian (EX-UE12), Jianyu (LI15), Jianzhen (SI9), Ashi (Extra) and Yanglingquan (GB34) on the affected side were selected. Canggui Tanxue needling technique, WN technique and EA were delivered in the MA group, the WN group and the EA group, respectively, 30 min each time, 3 times weekly for 4 weeks. The Neer test scores were compared；the visual analogue scale (VAS) was used to assess the degree of shoulder joint pain；the daily life activity abilities was evaluated using the activities of daily living (ADL) scale；the serum prostaglandin E2 (PGE2) content was measured using ELISA before and after treatment. The effectiveness rate and recurrence rate were calculated, and the occurrences of adverse reactions were recorded. RESULTS: Compared with the scores before treatment, the scores of pain, joint function, and range of motion as well as the total score of Neer test were all increased after treatment in the three groups (P<0.05)；the VAS score, ADL score and the content of serum PGE2 were decreased (P<0.05). After treatment, the pain score of Neer test in the EA group and the WN group were higher than those of the MA group (P<0.05), the joint function score of Neer test in the MA group and the WN group were higher than that of the EA group (P<0.05), and the range of motion score of Neer test in the MA group was higher when compared with the EA and WN groups (P<0.05). There was no statistical difference in the total score of Neer score among the three groups. VAS score in the EA group was lower than that of either the WN group or the MA group (P<0.05). ADL score in the MA group was lower compared with that of the WN group (P<0.05). PGE2 levels in both the WN group and the MA group were lower than that of the EA group (P<0.05). The total effective rate was 85.71% (30/35) in the MA group, 91.43% (32/35) in the EA group and 90.91% (30/33) in the WN group, there was no statistical differences among the three groups. At the end of the 6-month follow-up visit after treatment, there was no significant difference in the recurrence rate among three groups. No serious adverse reaction was found. CONCLUSIONS: In the treatment of CSP, the short-term effect is equivalent among EA, WN and MA. But, the analgesic effect is the best in the EA group, the treatment for anti-inflammation is the most effective in the MA and WN groups, and the needling technique of Canggui Tanxue in the MA group obtains the most favorable effect of releasing adhesion and recovering the range of motion in the shoulder joint.

A Multifunctional, Tough, Stretchable, and Transparent Curcumin Hydrogel with Potent Antimicrobial, Antioxidative, Anti-inflammatory, and Angiogenesis Capabilities for Diabetic Wound Healing.

The treatment of diabetic chronic wounds is still faced with great challenges, mainly due to wound infection, excessive inflammation, and peripheral vascular disease in the wound area. Therefore, it is of great importance to develop a novel multifunctional hydrogel with high efficiency to accelerate diabetic wound healing. Curcumin (Cur), a Chinese herbal, has shown great potential in enhancing the healing of diabetic chronic wounds because of its immunomodulatory and pro-angiogenic properties. However, its low aqueous solubility, poor bioavailability, and chemical instability have limited its clinical applications. To address these current bottlenecks, novel poly(vinyl alcohol) (PVA)-chitosan (CS)/sodium alginate (SA)-Cur (PCSA) hydrogels were prepared for the first time, and they demonstrated all of the above intriguing performances by the Michael addition reaction of CS and Cur. PCSA hydrogels show multiple dynamic bonds, which possess strong mechanical properties (tensile stress: ∼0.980 MPa; toughness: ∼258.45 kJ/m3; and compressive strength: ∼7.38 MPa at strain of 80%). These intriguing performances provided an optimal microenvironment for cell migration and proliferation and also promoted the growth of blood vessels, leading to early angiogenesis. Importantly, the experimental results demonstrated that PCSA hydrogels can effectively transform pro-inflammatory M1 macrophages into anti-inflammatory M2 macrophages without the need for additional ingredients in vitro. Benefiting from these characteristics, a full-thickness diabetic wound in a rat model demonstrated that PCSA hydrogels can effectively accelerate wound healing via ROS-scavenging, downregulation of IL-1ß, and upregulation of CD31 expression, resulting in angiogenesis and collagen deposition. This strategy not only provides a simple and safe Cur-based hydrogel for diabetic wound healing but also highlights the significant potential for the development of high-performance biomaterials for promoting diabetic wound healing using traditional Chinese medicine.

[Quality evaluation of salt-fired Eucommiae Cortex based on HPLC fingerprint, multi-component content determination, and chemometrics].

This study established an HPLC fingerprint and multi-component content determination method for salt-fired Eucommiae Cortex, and evaluated the quality of salt-fired Eucommiae Cortex from different sources using fingerprint similarity evaluation, cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least square discriminate analysis(OPLS-DA). HPLC was launched on a Cosmosil 5C_(18)-MS-Ⅱ column(4.6 mm×250 mm, 5 µm) by gradient elution with a mobile phase of methanol-0.2% phosphoric acid aqueous solution at a flow rate of 1.0 mL·min~(-1), detection wavelength of 238 nm, column temperature of 30 ℃, and an injection volume of 10 µL. The results of fingerprint similarity evaluation for 20 batches of salt-fired Eucommiae Cortex indicated that, except for batch S3 with a similarity of 0.893, the similarity of the other 19 batches was of ≥ 0.919, suggesting good similarity. Fourteen common peaks were calibrated and seven common peaks were identified including geniposidic acid. The mass fractions of geniposidic acid, chlorogenic acid, geniposide, genipin, pinoresinol diglucoside, liriodendrin, and pinoresinol-4-O-ß-D-glucopyranoside were 0.062 0%-0.426 9%, 0.024 9%-0.116 5%, 0.009 5%-0.052 9%, 0.005 5%-0.034 8%, 0.115 9%-0.317 8%, 0.016 4%-0.108 8%, and 0.026 4%-0.039 8%, respectively. Using CA, PCA, and OPLS-DA, the 20 batches of salt-fired Eucommiae Cortex were classified into three categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, two differential quality markers, geniposidic acid and chlorogenic acid, were identified. The established HPLC fingerprint and multi-component content determination method is stable and reliable, providing a reference for quality control of salt-fired Eucommiae Cortex.

Quantification and discovery of quality markers from Toddalia asiatica by UHPLC-MS/MS coupled with chemometrics.

INTRODUCTION: Toddalia asiatica (TA) is a classical traditional Chinese medicine used to treat rheumatoid arthritis and contusions. However, research regarding TA quality control is currently limited. OBJECTIVE: We aimed to establish a strategy for identifying quality markers that can be used for the evaluation of the quality of TA. METHOD: A rapid and efficient ultra-high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-MS/MS) method was developed for the quantitative determination of 19 compounds in TA from different regions. Then, the extraction process of TA was successively optimized by single-factor optimization and response surface methodology. Moreover, chemometrics was employed to confirm the correlation between quality and target compounds. RESULTS: Utilizing the UHPLC-MS/MS method, separation of the 19 bioactive compounds was achieved within 14 min. The method was validated in terms of linearity (r2 > 0.9982), precision (0.08%-3.70%), repeatability (0.50%-2.54%), stability (2.26%-5.46%), and recovery (95.8%-113%). The optimal extraction process (extraction solvent, 65% ethanol aqueous solution; solid-liquid ratio, 1:20; extraction time, 25 min) was determined with the total content of 19 bioactive compounds as indicator. Significant disparities were observed in the contents of target compounds across different batches of TA. Besides, all samples could be categorized into two distinct groups, and magnoflorine, (-)-lyoniresinol, nitidine chloride, norbraylin, skimmianine, and decarine were identified as quality markers. CONCLUSION: In the present study, we developed a strategy to improve the quality control of TA. In consideration of the pharmacodynamic activity and statistical differences, six compounds are proposed as quality markers for TA.

Bioactive Phosphorus Dendrimers as a Universal Protein Delivery System for Enhanced Anti-inflammation Therapy.

Nanocarrier-based cytoplasmic protein delivery offers opportunities to develop protein therapeutics; however, many delivery systems are positively charged, causing severe toxic effects. For enhanced therapeutics, it is also of great importance to design nanocarriers with intrinsic bioactivity that can be integrated with protein drugs due to the limited bioactivity of proteins alone for disease treatment. We report here a protein delivery system based on anionic phosphite-terminated phosphorus dendrimers with intrinsic anti-inflammatory activity. A phosphorus dendrimer termed AK-137 with optimized anti-inflammatory activity was selected to complex proteins through various physical interactions. Model proteins such as bovine serum albumin, ribonuclease A, ovalbumin, and fibronectin (FN) can be transfected into cells to exert their respective functions, including cancer cell apoptosis, dendritic cell maturation, or macrophage immunomodulation. Particularly, the constructed AK-137@FN nanocomplexes display powerful therapeutic effects in acute lung injury and acute gout arthritis models by integrating the anti-inflammatory activity of both the carrier and protein. The developed anionic phosphite-terminated phosphorus dendrimers may be employed as a universal carrier for protein delivery and particularly utilized to deliver proteins and fight different inflammatory diseases with enhanced therapeutic efficacy.

Isofraxidin attenuates dextran sulfate sodium-induced ulcerative colitis through inhibiting pyroptosis by upregulating Nrf2 and reducing reactive oxidative species.

BACKGROUND: Ulcerative colitis (UC), a non-specific gastrointestinal disease, is commonly managed with aminosalicylic acids and immunosuppressive agents to control inflammation and relieve symptoms, despite frequent relapses. Isofraxidin is a coumarin compound extracted from traditional Chinese medicine, exhibiting anti-inflammatory and antioxidant properties; however, its alleviating effect on UC remains unclear. Therefore, we investigated the mechanism of isofraxidin in lipopolysaccharide (LPS)-induced cell inflammation in human intestinal epithelial cell (HIEC) and human colorectal adenocarcinoma cells (Caco-2), as well as in dextran sulfate sodium (DSS)-induced UC in mice. METHODS: We established colitis models in HIEC and Caco-2 cells and mice with LPS and DSS, respectively. Additionally, NLRP3 knockout mice and HIEC cells transfected with NLRP3 silencing gene and ML385 illustrated the role of isofraxidin in pyroptosis and oxidative stress. Data from cells and mice analyses were subjected to one-way analysis of variance or a paired t-test. RESULTS: Isofraxidin significantly alleviated LPS-induced cell inflammation and reduced lactic dehydrogenase release. Isofraxidin also reversed DSS- or LPS-induced pyroptosis in vivo and in vitro, increasing the expression of pyroptosis-related proteins. Moreover, isofraxidin alleviated oxidative stress induced by DSS or LPS, reducing reactive oxidative species (ROS), upregulation nuclear factor erythroid 2-related factor 2 (Nrf2), and promoting its entry into the nucleus. Mechanistically, ML385 reversed the inhibitory effect of isofraxidin on ROS and increased pyroptosis. CONCLUSION: Isofraxidin can inhibit pyroptosis through upregulating Nrf2, promoting its entry into the nucleus, and reducing ROS, thereby alleviating DSS-induced UC. Our results suggest isofraxidin as a promising therapeutic strategy for UC treatment.

[Effects of Polystyrene Microplastics Combined with Cadmium Contamination on Soil Physicochemical Properties and Physiological Ecology of Lactuca sativa].

Contaminants such as microplastics (MPs) and heavy metals are commonly found in soils, both of which are extremely difficult to degrade and can easily form compound contamination, altering the physicochemical properties of the soil and thus potentially changing the growth and physiological and ecological characteristics of plants. In order to study the effects of the combined contamination of soil MPs and heavy metals on soil properties and plant growth, polystyrene microplastics (PS-MPs) with a particle size of 3 µm and the heavy metal cadmium were selected in the study. The changes in the physicochemical properties of soil and their effects on lettuce (Lactuca sativa) seed germination and seedling growth were studied at various exposure concentrations of PS-MPs (0, 10, 50, 100, 200, and 400 mg·kg-1) and combined with different Cd contamination concentrations (0, 1.2, and 6.0 mg·kg-1), respectively. The results showed that soil organic matter (SOM), available phosphorus (AP), alkali-hydrolysable nitrogen (AHN), and available kalium (AK) showed significant decreases as the intensity of PS-MPs combined with Cd contamination increased. Simultaneously, PS-MPs combined with Cd contamination also significantly reduced the germination rate of lettuce seeds, but low concentrations of PS-MPs slowed down the effect of Cd (6.0 mg·kg-1) contamination on lettuce seeds, and high concentrations of PS-MPs enhanced the effect of Cd (6.0 mg·kg-1). The fresh weight, dry weight, and plant height of lettuce seedlings showed an increasing and then decreasing trend with increasing exposure to PS-MPs. Chlorophyll content, superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) showed a decreasing trend, whereas malondialdehyde (MDA) content showed an overall increasing trend under different Cd concentrations. The main physicochemical indicators of the soil were negatively correlated with MDA of lettuce seedlings, whereas other indicators of the seedlings were positively correlated. The combined contamination of PS-MPs and Cd could affect the germination of plant seeds and the physiological and ecological characteristics of seedlings by changing the physicochemical properties of the soil. Both exposure to single PS-MPs contaminants and the combination of PS-MPs with Cd inhibited the germination of lettuce seeds and affected the physiological activities of their seedlings, and the inhibition was significantly increased with increasing exposure. Low exposure to PS-MPs or the combination of PS-MPs with Cd contamination exhibited a promotive effect on lettuce seedling growth. High exposure to PS-MPs combined with Cd contamination exhibited significant ecological effects on lettuce seedlings, and high exposure to PS-MPs exacerbated the ecotoxicological effects of Cd contaminants on lettuce seedlings, and PS-MPs and Cd exhibited synergistic effects. The results can provide some reference for assessing the ecological effects of MPs and heavy metal pollution in soil-plant systems.

A comprehensive review of the botany, ethnopharmacology, phytochemistry, pharmacology, quality control and other applications of Ligustici Rhizoma et Radix.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum sinense Oliv. and L. jeholense Nakai et Kitag. are globally recognized as medicinal botanical species, specifically the rhizomes and roots. These plant parts are collectively referred to as Ligustici Rhizoma et Radix (LReR), which is recorded in the Pharmacopoeia of the People's Republic of China (Ch. P). LReR enjoys widespread recognition in many countries such as China, Russia, Vietnam, and Korea. It is an herbal remedy traditionally employed for dispelling wind and cold, eliminating dampness, and alleviating pain. Numerous bioactive compounds have been successfully isolated and identified, displaying a diverse array of pharmacological activities and medicinal value. THE AIM OF THE REVIEW: This review aims to primarily center on the botanical aspects, ethnopharmacology, phytochemistry, pharmacology, toxicity, quality control, and other applications of LReR to furnish a comprehensive and multidimensional foundation for future exploration and utilization. MATERIALS AND METHODS: Relevant information about LReR was acquired from ancient books, doctoral and master's dissertations, Google Scholar, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), ScienceDirect, classical literature, and clinical reports. Several electronic databases were also incorporated. RESULTS: In traditional usage, LReR had been traditionally employed for the treatment of anemofrigid headaches, colds, and joint pain. It possessed therapeutic properties for facial skin disorders, thereby facilitating skin regeneration. It has been subjected to comprehensive chemical analysis, resulting in the identification and isolation of 190 compounds, including phthalides, phenylpropanoids, flavonoids, phenolic acids, triterpenes, steroids, volatile oil, fatty acids, and other constituents. The pharmacological activities have been in-depth explored through modern in vivo and in vitro studies, confirming its anti-inflammatory, analgesic, and anti-melanin effects. Furthermore, it exhibited pharmacological activities such as antioxidant, anticancer, antibacterial, and vasodilatory properties. This study provides a basic to contribute to the advancement of research, medicinal applications and product development related to LReR. CONCLUSIONS: Considering its traditional and contemporary applications, phytochemical composition, and pharmacological properties, LReR was regarded as a valuable botanical resource for pharmaceutical and pest control purposes. While certain constituents had demonstrated diverse pharmacological activities and application potential, further elucidation was required to fully understand their specific actions and underlying mechanisms. Hence, there was a need to conduct additional investigations to uncover its material foundation and mode of action.

The comparative analysis of Lonicerae Japonicae Flos and Lonicerae Flos: A systematical review.

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae Japonicae Flos (LJF) and Lonicerae Flos (LF) were once used as the same herb in China, but they were distinguished by Chinese Pharmacopoeia in 2005 in terms of their medicinal history, plant morphology, medicinal properties and chemical constituents. However, their functions, flavor, and meridian tropism are the same according to the Chinese pharmacopoeia 2020 edition, making researchers and customers confused. AIM OF THE REVIEW: This review aimed to provide a comparative analysis of LJF and LF in order to provide a rational application in future research. MATERIALS AND METHODS: The information was gathered from China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations (all chosen articles were reviewed attentively from 1980.1 to 2023.8). RESULTS: Till now, 507 chemical compounds have been isolated and identified in LJF, while 223 ones (79 overlapped compounds) are found in LF, including organic acids and derivatives, flavonoids, triterpenoids, iridoids, and essential oil components, etc. In addition, the pharmacological activities of LJF and LF, especially for their anti-influenza efficacy and mechanism, and their difference in terms of pharmacokinetic parameters, toxicology, and clinical applications were also summarized. CONCLUSION: The current work offers comparative information between LJF and LF in terms of botany, traditional uses, phytochemistry, ethnopharmacology, pharmacokinetics, toxicology, and pharmacology, especially their anti-influenza activities. Despite the same clinical applications and similar chemical components in LJF and LF, differentiated components were still existed, resulting in differentiated pharmacological activities and pharmacokinetics parameters. Moreover, the research about anti-influenza mechanism and functional substances of LJF and LF is dramatically limited, restricting their clinical applications. In addition, few studies have investigated the metabolism feature of LF in vivo, which is one of the important bases for revealing the pharmacological mechanism of LF. At the same time, the toxicity of LJF and LF is not fully studied, and the toxic compounds of LJF and LF need to be screened out in order to standardize the drug use and improve their rational applications.