Chemistry, pharmacokinetics, pharmacological activities, and toxicity of Quercitrin.

Quercitrin is a naturally available type of flavonoid that commonly functions as the dietary ingredient and supplement. So far, a wide spectrum of bioactivities of quercitrin have been revealed, including antioxidative stress, antiinflammation, anti-microorganisms, immunomodulation, analgesia, wound healing, and vasodilation. Based on these various pharmacological activities, increasing studies have focused on the potency of quercitrin in diverse diseases in recent years, such as bone metabolic diseases, gastrointestinal diseases, cardiovascular and cerebrovascular diseases, and others. In this paper, by collecting and summarizing publications from the recent years, the natural sources, pharmacological activities and roles in various diseases, pharmacokinetics, structure-activity relationship, as well as the toxicity of quercitrin were systematically reviewed. In addition, the underlying molecular mechanisms of quercitrin in treating related diseases, the dose-effect relationships, and the novel preparations were discussed on the purpose of broadening the application prospect of quercitrin as functional food and providing reference for its clinical application. Notably, clinical studies of quercitrin are insufficient at present, further high-quality studies are needed to firmly establish the clinical efficacy of quercitrin.

Human infection with an avian influenza A (H9N2) virus in the middle region of China.

During the epidemic period of the novel H7N9 viruses, an influenza A (H9N2) virus was isolated from a 7-year-old boy with influenza-like illness in Yongzhou city of Hunan province in November 2013. To identify the possible source of infection, environmental specimens collected from local live poultry markets epidemiologically linked to the human case in Yongzhou city were tested for influenza type A and its subtypes H5, H7, and H9 using real-time RT-PCR methods as well as virus isolation, and four other H9N2 viruses were isolated. The real-time RT-PCR results showed that the environment was highly contaminated with avian influenza H9 subtype viruses (18.0%). Sequencing analyses revealed that the virus isolated from the patient, which was highly similar (98.5-99.8%) to one of isolates from environment in complete genome sequences, was of avian origin. Based on phylogenetic and antigenic analyses, it belonged to genotype S and Y280 lineage. In addition, the virus exhibited high homology (95.7-99.5%) of all six internal gene lineages with the novel H7N9 and H10N8 viruses which caused epidemic and endemic in China. Meanwhile, it carried several mammalian adapted molecular residues including Q226L in HA protein, L13P in PB1 protein, K356R, S409N in PA protein, V15I in M1 protein, I28V, L55F in M2 protein, and E227K in NS protein. These findings reinforce the significance of continuous surveillance of H9N2 influenza viruses.

Dynamic assessment of community resilience in China: empirical surveys from three provinces.

Background: Strengthening the construction of community resilience and reducing disaster impacts are on the agenda of the Chinese government. The COVID-19 pandemic could alter the existing community resilience. This study aims to explore the dynamic change trends of community resilience in China and analyze the primary influencing factors of community resilience in the context of COVID-19, as well as construct Community Resilience Governance System Framework in China. Methods: A community advancing resilience toolkit (CART) was used to conduct surveys in Guangdong, Sichuan, and Heilongjiang provinces in China in 2015 and 2022, with community resilience data and information on disaster risk awareness and disaster risk reduction behaviors of residents collected. The qualitative (in-depth interview) data from staffs of government agencies and communities (n = 15) were pooled to explore Community Resilience Governance System Framework in China. Descriptive statistics analysis and t-tests were used to investigate the dynamic development of community resilience in China. Hierarchical regression analysis was performed to explore the main influencing factors of residential community resilience with such socio-demographic characteristics as gender and age being controlled. Results: The results indicate that community resilience in China has improved significantly, presenting differences with statistical significance (p < 0.05). In 2015, connection and caring achieved the highest score, while disaster management achieved the highest score in 2022, with resources and transformative potential ranking the lowest in their scores in both years. Generally, residents presented a high awareness of disaster risks. However, only a small proportion of residents that were surveyed had participated in any "community-organized epidemic prevention and control voluntary services" (34.9%). Analysis shows that core influencing factors of community resilience include: High sensitivity towards major epidemic-related information, particular attention to various kinds of epidemic prevention and control warning messages, participation in epidemic prevention and control voluntary services, and formulation of epidemic response plans. In this study, we have constructed Community Resilience Governance System Framework in China, which included community resilience risk awareness, community resilience governance bodies, community resilience mechanisms and systems. Conclusion: During the pandemic, community resilience in China underwent significant changes. However, community capital was, is, and will be a weak link to community resilience. It is suggested that multi-stages assessments of dynamic change trends of community resilience should be further performed to analyze acting points and core influencing factors of community resilience establishment at different stages.

[Experimental study on two-way application of drugs with neutral property for promoting blood circulation and removing blood stasis on cold and heat blood stasis syndromes II].

OBJECTIVE: To further study the characteristics of drugs with neutral property in two-way application and conditioned dominance by observing the action characteristic of 10 traditional Chinese medicines with neutral property in hemorheological indicators of heat stagnation and blood stasis syndrome and cold stagnation and blood stasis syndrome rats. METHOD: The model of heat stagnation and blood stasis syndrome rats was established by injecting carrageenan and dry yeast, while the model of cold stagnation and blood stasis syndrome rats was established by body freezing. Subsequently, 10 traditional Chinese medicines with neutral property, 5 traditional Chinese medicines with heat property and 5 traditional Chinese medicines with cold property were selected for intervention to observe the changes in such indicators as whole blood viscosity, plasma viscosity and hematocrit and analyze the action characteristics of drugs with neutral property. RESULT: ANOVA showed that among six of the 10 traditional Chinese medicines with neutral property, including Typhae Pollen, Sarcandrae Herba and Sappan lignum, could obviously increase the hemorheological indicators of both heat stagnation and blood stasis syndrome and cold stagnation and blood stasis syndrome rats; five traditional Chinese medicines with cold property, such as Salviae Miltiorrhizae Radix et Rhizoma, Leonuri Herba, Rhei Radix et Rhizoma, could significantly ameliorate the hemorheological indicators of heat stagnation and blood stasis syndrome rats (P < 0.01 or P < 0.05), and Salvia Miltiorrhiza Radix et Rhizoma alone could ameliorate the hemorheological indicators of cold stagnation and blood stasis syndrome rats (P < 0.05); all of the five traditional Chinese medicines with heat property could significantly ameliorate the hemorheological indicators of cold stagnation and blood stasis syndrome rats (P < 0.01), among which Carthami Flos and Notoginseng Radix et Rhizoma could significantly ameliorate the hemorheological indicators of cold stagnation and blood stasis syndrome rats. According to the average high-shear blood viscosity analysis, drugs with neutral property showed similar action characteristics to those with cold property in ameliorating hemorheology indicators of heat stagnation and blood stasis syndrome rat and better effect than those with heat property in reducing whole blood viscosity; and traditional Chinese medicines with neutral property have the similar action characteristics to those with heat property in improving the hemorheology indicators of cold stagnation and blood stasis syndrome rat and better effect than those with heat property in reducing whole blood viscosity. CONCLUSION: Under the condition of heat stagnation and blood stasis syndrome, traditional Chinese medicines with neutral property show the similar action characteristics to those with cold property; but under the condition of cold stagnation and blood stasis syndrome, traditional Chinese medicines with neutral property show the similar action characteristics to those with heat property. This indicates that traditional Chinese medicines with neutral property show both heat and cold properties under he conditions of heat stagnation and blood stasis syndrome and cold stagnation and blood stasis syndrome.

Laggera alata Attenuates Inflammatory Response by Regulating Macrophage Polarization in Rheumatoid Arthritis Mice.

Rheumatoid arthritis (RA) is a type of joint injury, which can induce the activation of inflammatory factors and polarization of tissue macrophages. Total phenolics from Laggera alata (TPLA) has been reported to exhibit anti-inflammatory effect in various diseases. However, its specific function in RA is still unknown. Here, the protective properties of TPLA were studied in collagen-induced arthritis (CIA)-induced RA mice. RA mouse model was established through the CIA induction. Arthritis score, hind paw thickness, and the body weight of the RA mice were evaluated in each group. H&E staining was conducted in hind paw and joint tissues for histopathological staining. The distal femur was analyzed by microCT, and bone loss-related indicators were assessed. The expression of macrophage polarization markers was detected by immunofluorescence staining in RA mice. The serum levels of inflammatory markers were determined by enzyme-linked immunosorbent assay (ELISA). TPLA reduced the CIA-induced arthritis score and hind paw thickness in mice. The body weight of the CIA mouse was significantly increased by TPLA treatment. TPLA improved the CIA-induced histopathological changes in the hind paw and joint tissues from the mice. TPLA inhibited the bone loss and alleviated bone destruction in CIA mouse model. TPLA altered the macrophage phenotype from M1 macrophages into M2 in CIA mice. TPLA suppressed the levels of inflammatory markers both in the serum and joint tissues of the CIA mice. TPLA mitigated RA development by suppressing inflammatory reaction through the inhibition of M1 microphage polarization.

Total flavonoids extracted from Penthorum chinense Pursh mitigates CCl4-induced hepatic fibrosis in rats via inactivation of TLR4-MyD88-mediated NF-κB pathways and regulation of liver metabolism.

Background: Penthorum chinense Pursh (PCP) is widely utilized in China to treat a variety of liver diseases. It has been shown that flavonoids inhibit inflammation and have the potential to attenuate tissue damage and fibrosis. However, the mechanisms underlying how total flavonoids isolated from PCP (TFPCP) exert their anti-fibrotic effects remain unclear. Methods: The chemical composition of TFPCP was determined using UHPLC-Q-Orbitrap HRMS. Subsequently, rats were randomly assigned to a control group (Control), a carbon tetrachloride (CCl4)-induced hepatic fibrosis model group (Model), a positive control group [0.2 mg/(kg∙day)] of Colchicine), and three TFPCP treatment groups [50, 100, and 150 mg/(kg∙day)]. All substances were administered by gavage and treatments lasted for 9 weeks. Simultaneously, rats were intraperitoneally injected with 10%-20% CCl4 for 9 weeks to induce liver fibrosis. At the end of the experiment, the liver ultrasound, liver histomorphological, biochemical indicators, and inflammatory cytokine levels were tested respectively. The underlying mechanisms were assessed using Western blot, immunohistochemistry, immunofluorescence, RT-qPCR, and metabolomics. Results: Fourteen flavonoids were identified in TFPCP. Compared with control animals, CCl4-treated rats demonstrated obvious liver injury and fibrosis, manifested as increases in gray values, distal diameter of portal vein (DDPV) and a decrease in blood flow velocity (VPV) in the ultrasound analysis; increased biochemical index values (serum levels of ALT, AST, TBIL, and ALP); marked increases in the contents of fibrotic markers (PC III, COL4, LN, HA) and inflammatory factors (serum TNF-α, IL-6, and IL-1ß); and significant pathological changes. However, compared with the Model group, the ultrasound parameters were significantly improved and the serum levels of inflammatory cytokines were reduced in the TFPCP group. In contrast, the expression of TGF-ß1, TLR4, and MyD88, as well as the p-P65/P65 and p-IκBα/IκBα ratios, were considerably reduced following TFPCP treatment. In addition, we identified 32 metabolites exhibiting differential abundance in the Model group. Interestingly, TFPCP treatment resulted in the restoration of the levels of 20 of these metabolites. Conclusion: Our findings indicated that TFPCP can ameliorate hepatic fibrosis by improving liver function and morphology via the inactivation of the TLR4/MyD88-mediated NF-κB pathway and the regulation of liver metabolism.

The mechanism of action of safflower total flavonoids in the treatment of endometritis caused by incomplete abortion based on network pharmacology and 16S rDNA sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: Safflower is a traditional Chinese medicine used for treating gynaecological diseases. However, its material basis and mechanism of action in the treatment of endometritis induced by incomplete abortion are still unclear. AIM OF THE STUDY: This study aimed to reveal the material basis and mechanism of action of safflower in the treatment of endometritis induced by incomplete abortion through comprehensive methods, including network pharmacology and 16S rDNA sequencing. MATERIALS AND METHODS: Network pharmacology and molecular docking methods were used to screen the main active components and potential mechanisms of action of safflower in the treatment of endometritis induced by incomplete abortion in rats. A rat model of endometrial inflammation by incomplete abortion was established. The rats were treated with safflower total flavonoids (STF) based on forecasting results, serum levels of inflammatory cytokines were analysed, and immunohistochemistry, Western blots, and 16S rDNA sequencing were performed to investigate the effects of the active ingredient and the treatment mechanism. RESULTS: The network pharmacology prediction results showed 20 active components with 260 targets in safflower, 1007 targets related to endometritis caused by incomplete abortion, and 114 drug-disease intersecting targets, including TNF, IL6, TP53, AKT1, JUN, VEGFA, CASP3 and other core targets, PI3K/AKT, MAPK and other signalling pathways may be closely related to incomplete abortion leading to endometritis. The animal experiment results showed that STF could significantly repair uterine damage and reduce the amount of bleeding. Compared with the model group, STF significantly down-regulated the levels of pro-inflammatory factors (IL-6, IL-1ß, NO, TNF-α) and the expression of JNK, ASK1, Bax, caspase3, and caspase11 proteins. At the same time, the levels of anti-inflammatory factors (TGF-ß and PGE2) and the protein expression of ERα, PI3K, AKT, and Bcl2 were up-regulated. Significant differences in the intestinal flora were seen between the normal group and the model group, and the intestinal flora of the rats was closer to the normal group after the administration of STF. CONCLUSIONS: The characteristics of STF used in the treatment of endometritis induced by incomplete abortion were multi-targeted and involved multiple pathways. The mechanism may be related to the activation of the ERα/PI3K/AKT signalling pathway by regulating the composition and ratio of the gut microbiota.

Network pharmacology identification and in Vivo validation of key pharmacological pathways of Phyllanthus reticulatus (Euphorbiaceae) leaf extract in liver cancer treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus reticulatus (Euphorbiaceae) is a medicinal plant that has been used in Zhuang medicine since ancient times. Traditionally, it has the effect of removing toxins and detumescence and can be used to treat hepatitis in China and India. Our previous studies have proved that the ethyl acetate extract of its leaves (PRPE) has an anti-hepatoma effect. AIM OF THE STUDY: To predict targets of an ethyl acetate extract of Phyllanthus reticulatus leaves (PRPE) in hepatoma treatment via network pharmacology and verify the predictions in a mouse model of liver cancer. MATERIALS AND METHODS: Chemical constituents and therapeutic targets of P. reticulatus (PRP) were searched and predicted via public databases. A protein-protein interaction network comprising common targets was constructed, and the key gene targets were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for biological function and pathway enrichment analyses. The effects of PRP on BEL-7404 and HepG2 cells were determined by MTT assay, apoptosis was measured by flow cytometry and hoechst44432/PI. And a nude mouse xenograft model was established to verify the anti-tumour effect in vivo. The histopathology of tumours was observed by staining with haematoxylin and eosin (H&E). Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to determine the gene and protein expression levels of phosphoinositide 3-kinase (PI3K), Akt1, p53, caspase-3, Bcl-2 and Bax, respectively. RESULTS: Twenty-seven chemical components and 567 potential therapeutic targets of PRP were identified. GO analysis indicated that these targets are mainly associated with peptidyl-tyrosine phosphorylation and steroid metabolic process. KEGG analysis showed that the targets are mainly located in the PI3K/Akt, apoptosis, mitogen-activated protein kinase (MAPK), Ras and vascular endothelial growth factor (VEGF) signalling pathways. According to the p-adjust value, the PI3K/Akt pathway is the core pathway. In vitro, PRPE could inhibit proliferation and induce apoptosis in hepatoma cells. IC50 values of PRPE were 2.48 and 6.34 mg/mL for BEL-7404 and hepG2 cells, respectively. PRPE significantly reduced tumour volume and weight. H&E results showed that PRPE repaired necrotic areas in hepatoma cells. PRPE reduced the protein expression of PI3K, Akt1 and Bcl-2 and increased the protein expression of p53 and Bax. Meanwhile, PRPE reduced the mRNA expression of PI3K, AKT1 and BCL2 and increased the mRNA expression of TP53, CASP3 and BAX. CONCLUSION: The targets of PRPE are the PI3K/Akt, apoptosis, MAPK, Ras and VEGF signalling pathways. Passing through the PI3K/Akt pathway to induce apoptosis is the main mechanism of PRPE.

Pharmacological Activities of Safflower Yellow and Its Clinical Applications.

Background: Safflower is an annual herb used in traditional Chinese herbal medicine. It consists of the dried flowers of the Compositae plant safflower. It is found in the central inland areas of Asia and is widely cultivated throughout the country. Its resistance to cold weather and droughts and its tolerance and adaptability to salts and alkalis are strong. Safflower has the effect of activating blood circulation, dispersing blood stasis, and relieving pain. A natural pigment named safflower yellow (SY) can be extracted from safflower petals. Chemically, SY is a water-soluble flavonoid and the main active ingredient of safflower. The main chemical constituents, pharmacological properties, and clinical applications of SY are reviewed in this paper, thereby providing a reference for the use of safflower in preventing and treating human diseases. Methods: The literature published in recent years was reviewed, and the main chemical components of SY were identified based on chemical formula and structure. The pharmacological properties of hydroxysafflor yellow A (HSYA), SYA, SYB, and anhydrosafflor yellow B (AHSYB) were reviewed. Results: The main chemical constituents of SY included HSYA, SYA, SYB, and AHSYB. These ingredients have a wide range of pharmacological activities. SY has protective effects on the heart, kidneys, liver, nerves, lungs, and brain. Moreover, its effects include, but are not limited to, improving cardiovascular and cerebrovascular diseases, abirritation, regulating lipids, and treating cancer and diabetic complications. HSYA is widely recognised as an effective ingredient to treat cardiovascular and cerebrovascular diseases. Conclusion: SY has a wide range of pharmacological activities, among which improving cardiovascular and cerebrovascular diseases are the most significant.

Update on Pharmacological Activities, Security, and Pharmacokinetics of Rhein.

Rhein, belonging to anthraquinone compounds, is one of the main active components of rhubarb and Polygonum multiflorum. Rhein has a variety of pharmacological effects, such as cardiocerebral protective effect, hepatoprotective effect, nephroprotective effect, anti-inflammation effect, antitumor effect, antidiabetic effect, and others. The mechanism is interrelated and complex, referring to NF-κB, PI3K/Akt/MAPK, p53, mitochondrial-mediated signaling pathway, oxidative stress signaling pathway, and so on. However, to some extent, its clinical application is limited by its poor water solubility and low bioavailability. Even more, rhein has potential liver and kidney toxicity. Therefore, in this paper, the pharmacological effects of rhein and its mechanism, pharmacokinetics, and safety studies were reviewed, in order to provide reference for the development and application of rhein.