The biological behavior of carbon dots, especially the mechanism of cellular uptake and intracellular distribution, is the basis of its biomedical applications. In this paper, blue fluorescent carbon quantum dots were synthesized by hydrothermal method with Poria cocos polysaccharide as raw material, and the specific biological behavior of carbon dots entering cells was explored to evaluate its biological activity. It was characterized by transmission electron microscopy, UV-vis absorption spectroscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Two different cell lines, immunocytes-RAW264.7 cells (mouse mononuclear macrophages cells) and cancer cells-4T₁ cells (mouse breast cancer cells), were used as the research objects to study the uptake kinetics, uptake pathway, distribution and efflux of polysaccharide carbon dots in cells. The results showed that the carbon dots have a size distribution of 2 to 10 nm, and the average size was 6.85 nm. The carbon dots were mainly composed of C, O and N elements, with abundant surface functional groups such as -OH, C=O, C-N and C=C, and the fluorescence quantum yield was 4.72%. Carbon dots enter cells in a certain concentration and time dependence. Different cell lines have different uptake pathways. RAW264.7 cells enter the cells mainly by macrophage-specific phagocytosis, and a small part of the endocytosis is mediated by caveolin, while 4T₁ cells are mainly mediated by grid protein endocytosis and giant cell drinking process. In summary, the synthesized carbon dots have good fluorescence properties, low cytotoxicity and excellent biocompatibility, which can be used for cell imaging applications.

An analytical method was developed for determination of 7 aminoglycosides antibiotics in bear bile powder by hydrophilic interaction liquid chromatography tandem mass spectrometry. The samples were purified by mix-mode weak cation exchange and reversed-phase SPE. Waters ACQUITY UPLC BEH Amide column (100 mm × 3.0 mm, 1.7 μm) was used with 0.2% formic acid aqueous solution-0.2% formic acid acetonitrile solution as mobile phases by gradient elution. The aminoglycosides were detected by electrospray ionization mass spectrometry in positive mode with multiple reaction monitoring (MRM) mode. Spectinomycin, streptomycin, amikacin, kanamycin, tobramycin, apramycin and neomycin possessed good linear correlation in the respective concentration ranges, with the correlation coefficients more than 0.99. The mean recoveries at 3 spiked levels were in the range of 61.3%~127.3%, and the RSDs were 0.1%~1.9%. The limits of quantification were 0.2~1.0 mg·kg^-1. The method had been applied to the analysis of actual samples.

Hepatotoxicity induced by herbal medicines such as Gynura japonica, which contains large amount of pyrrolizidine alkaloids (PAs) such as senecionine (SEN), is among the most serious problems of herbal drug-induced liver injury, yet there is no effective treatment in clinic. We have previously reported that ritonavir (the well-known CYP3A4 inhibitor) protected rats against Gynura japonica-induced liver injury in rats, which was closely related to the inhibition of the metabolic activation of PAs. A large number of lignans have been identified in Schisandrae Chinensis Fructis and are reported to attenuate drug-induced liver injuries by modulating the drug metabolism enzymes. Therefore, the present study investigated the protective effect and potential mechanism of schisandrol A (SoA, a representative lignan identified in Schisandrae Chinensis Fructis) against SEN-induced hepatotoxicity in mice. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine (PZSHUTCM210604002). Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine. Liver injury was induced by a single gavage of SEN (150 μmol·kg^-1); mice in the protection group were gavaged with SoA (116 μmol·kg^-1) 7 days before SEN treatment. The results show that SoA dramatically alleviated SEN-induced liver injury in mice. Mice in the protection group showed decreased serum activities for alanine aminotransferase and aspartate aminotransferase; in addition, the hepatic necrosis and sinusoidal hemorrhage in SEN-treated mice were markedly attenuated in the protection group. The serum contents of SEN metabolites in mice were decreased. In vitro studies were performed by using human liver microsomes and proved that SoA inhibits CYP3A4 to decrease the metabolism of SEN. These studies indicate that SoA attenuated SEN-induced liver injury in mice, which was closely related to the inhibition of the metabolic activation of SEN. These results provide a better understanding of the relationship between CYP3A4 and PA-induced toxicity. This work also will be helpful in developing effective treatments for SEN-induced liver injury based on inhibition of its metabolic activation, and in making reasonable evaluations of the safety of herbal medicines containing PAs such as G. japonica.

In this study, the molecular mechanism of Cinnamomi Cortex-Rehmanniae Radix (CR) in the prevention and treatment of osteoporosis (OP) was investigated by integrating compatibility analysis of compound, bioinformatics and metabolomics. The rat OP models were established, and the Micro-CT indexes and pathological sections were comprehensively evaluated. The results showed that compared with the model group, the indexes such as bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly increased after CR treatment (P < 0.05), and the bone trabeculae were arranged into mesh. The results of UHPLC-Q-TOF/MS mainly involved amino acid metabolism, lipid metabolism and estrogen metabolism pathways. Integrating bioinformatics and metabolomics analysis, it was finally found that: ① cinnamic acid and ethylcinnamate inhibit inflammatory factors such as TNF, IL-1β, and IL-13, thereby preventing and treating OP; ② multiple active ingredients of CR target ESR2, PPARG, and CYP19A1, GABRA1 and other targets, regulate cAMP synthesis, AMPK signaling pathway and lipid metabolism, thereby regulating estrogen levels to prevent and treat OP; ③ oleic acid, arachic acid, etc. act on AR, VDR and other targets, and regulate HIF-1 signaling pathway and AGE-RAGE signaling pathway, thereby regulating osteoblasts and osteoclasts, and affecting calcium and phosphorus absorption to maintain bone homeostasis. This study clarified the molecular mechanism of CR in preventing and treating OP from the perspective of multi-directional regulation of inflammatory factors, estrogen and bone homeostasis, and provided theoretical basis for the clinical application of CR and the development of compound. This experiment complied with the ethical standards of animal experiments and was approved by the Animal Ethics Committee of Shaanxi University of Chinese Medicine (No. SUCMDL20210309002).

This study investigated the protective effect and related mechanisms of Xinhui citrus fermentation liquor on mice with ulcerative colitis. Animal experiments follow the rules of Animal Ethics Committee of Southern Medical University. C57BL/6 mice were given 3% dextran sodium sulfate (DSS) for 6 days to induce acute ulcerative colitis. During this period, Xinhui citrus fermentation liquor, decoction of Citrus reticulata blanco (both orally administrated with 300 mg·kg^-1·d^-1 crude polysaccharide) or positive drug 5-aminosalicylic acid (100 mg·kg^-1·d^-1) were gavaged continuously for 9 days. Cecal contents were collected for 16S rRNA sequencing analysis. The levels of inflammatory factors, tight junction proteins and nuclear factor erythroid 2 related factor 2 / Nod-like receptor protein 3 (Nrf2/NLRP3) pathway related proteins in the colon were detected by real-time PCR (RT-PCR), immunofluorescence and Western blot. Our results showed that Xinhui citrus fermentation liquor and Citrus reticulata blanco protected against UC-induced weight loss, diarrhea, bloody stool, and colon shortening. The mRNA and protein levels of pro-inflammatory factors, such as interleukin 6 (Il-6) and CXC chemokine ligand 10 (Cxcl10) and NLRP3 inflammasome were significantly decreased; the mRNA levels of colon anti-inflammatory factor (Il-10), tight junction protein [zonula occludens-1 (Zo-1), occludin, claudin-1], mucin 2 (Muc2), Nrf2, as well as the mRNA and protein levels of NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) were significantly increased. In addition, Xinhui citrus fermentation liquor increased the abundance of Akkermansia and reduced the abundance of harmful bacteria Enterococcus and Streptococcus. The correlation analysis showed that the abundance of Akkermansia was positively correlated with anti-inflammatory factors, tight junction protein and the related genes levels of Nrf2 signaling pathway. In summary, Xinhui citrus fermentation liquor ameliorates acute ulcerative colitis in mice via regulating intestinal bacteria homeostasis and Nrf2/NLRP3 pathway to repair intestinal mucosa.

A new compound was isolated from the 95% ethanolic extract of the rhizomes of Curcuma longa L. using silica gel column chromatography, medium pressure liquid chromatography, and semi-preparative high performance liquid chromatography. The structure and absolute configuration of the compound was elucidated by HR-ESI-MS, NMR, and electronic circular dichroism (ECD) calculations. It is a novel sesquiterpenoid, which is named as isoturmeronol B (1). The carbon skeleton of compound 1 is similar to that of bisabolane-type sesquiterpenoid. The only difference is that the methyl group at C-4 in bisabolene-type sesquiterpenoid is migrated to C-5 in compound 1. Besides, the anti-inflammatory and antioxidant activities of the compound 1 were evaluated. The results showed that 1 has no anti-inflammatory and antioxidant activities.

To investigate the chemical constituents of Anisodus tanguticus, silica gel column chromatography, Sephadex LH-20 column chromatography, preparative thin layer chromatography, and semi-preparative HPLC were used to separate and purify the chemical constituents from the extract of A. tanguticus. The planar structure of the isolated compound was identified by HRMS, IR, and 2D NMR experiments. The absolute configuration of the isolated compound was determined by a combination of NOESY, coupling constant, circular dichroism (CD), and transition metal chelate reagent dimolybdenum tetraacetate [Mo₂(OAc)₄]-induced circular dichroism (ICD) data analysis. A new compound of the anisotane-type sesquiterpene (1) was isolated, which was determined to be (1R, 2S, 3R, 4R, 6R, 7R, 9R)-anisotane-11(13)-ene-3, 4, 9-triol and named anisotanol F. This is the second report of anisotane-type sesquiterpene, which has previously been reported as a novel sesquiterpenoid skeleton by our research group. Furthermore, the cytotoxicity against HUVECs and inhibitory effect on NO release in LPS-induced RAW264.7 cells of compound 1 were investigated. However, the results showed that it was inactive. Compound 1 is a new compound isolated from A. tanguticus. It belongs to the unusual anisotane-type sesquiterpene. This result enriches the chemical composition of A. tanguticus.

Histone deacetylase (HDAC) is usually abnormally overexpressed, which mainly leads to the transcriptional repression of tumor suppressor genes. Histone deacetylase inhibitors (HDIs) exert anti-tumor biological effects by regulating nucleosome structure, inhibiting HDAC activity, and controlling the expression of tumor suppressor genes. There are currently 5 drugs on the market, but only for peripheral T-cell lymphoma and cutaneous T-cell lymphoma. In solid tumors, most of the HDAC inhibitors used have failed to achieve effective therapeutic effects. Phosphoinositide 3-kinase (PI3K) is the starting node of the PI3K-AKT-mTOR signaling pathway, which plays a very important role in the proliferation, migration, invasion, and differentiation of tumor cells. The abnormal activation of PI3K is closely related to the occurrence and development of tumors, and the combined use of HDAC and PI3K inhibitors and HDAC/PI3K dual-target inhibitors show synergistic anticancer activity. This article introduces the anti-tumor clinical and preclinical research progress of representative HDAC inhibitors and PI3K inhibitors, as well as HDAC/PI3K dual-target inhibitors.

In traditional oral practice, the presystemic interactions with gut microbiota is an important mechanism underlying the holistic health benefits of Chinese herbal medicines (CHMs), making the study of CHMs distinct from the research of Western medicines of which the systemic exposure (level in blood) is the starting point and the core. Gut microbial metabolism complements host metabolism in maintaining metabolic homeostasis of many biologically important endogenous molecules and the disposition of numerous exogenous compounds. Among them, the widely distributed gut bacterial β-glucuronidases (BGUSs) coordinate with host UDP-glucuronosyltransferases (UGTs) to play a role in the occurrence and intervention of diseases by affecting the glucuronidation homeostasis and altering the intestinal local and/or systemic exposure of endogenous compounds and xenobiotics. On one hand, many ingredients of CHMs undergo enterohepatic circulation; On the other hand, CHMs can act on BGUSs directly or indirectly change the distribution and function of BGUSs through reprogramming gut microbiome. The multiple interactions between BGUSs and CHMs may play an important role in the overall therapeutic benefits of CHMs. This work firstly summarizes the latest research progress on BGUSs; then the physiological, pathological and pharmacological significance of BGUSs are exemplified with representative endogenous and exogenous compounds from the aspects of nutrient utilization, metabolic homeostasis, and therapeutic response based on the varied substrate spectra of BGUSs; finally, the scattered data in literature were integrated to summarize the multiple interactions between BGUSs and CHMs, highlighting the important role of BGUSs in the holistic actions of CHMs.

In this study, black phosphorus nanosheets (BP) were prepared by the ordinary liquid phase method, and resveratrol was loaded on the BP after being modified by polyethylene glycol. The brain targeting of BP was investigated by fluorescent protein labeling, and the effects of black phosphorus on cerebral ischemia/reperfusion injury were studied by 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, neurobehavioral evaluation, and brain edema. Protein immunoblotting analysis was used to explore the molecular mechanism of the BP drug delivery system on ischemic brain injury. Hemolysis test and hematoxylin-eosin (H & E) staining were used to evaluate its biocompatibility. The results showed that BP had excellent drug loading capacity, uniform drug loading system structure and particle size, stable drug release curve, and excellent photothermal effect. Through the analysis and comparison of fluorescence intensity, it was found that BP can increase the permeability of blood-brain barrier (BBB) under the condition of near-infrared light assisted irradiation, and make drugs more pass through the BBB. In addition, the black phosphorus nano tablet drug delivery system can significantly improve the neurobehavioral disorder of mice after modeling, and the cerebral infarction area and brain edema degree are significantly decreased. Western blot experiments showed that the drug delivery system could play an anti-ischemic brain injury role by activating the expression of antioxidant signaling pathway proteins nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). The hemolysis test and H & E test results of the BP drug carrier system showed that it had no obvious toxicity and high safety. In conclusion, the BP prepared in this study had high drug loading, good photothermal performance, and high safety. Under the near-infrared condition, they also have certain brain targeting ability, which can improve the therapeutic effect of drugs in the brain. Animal welfare and experimental procedures were following the regulations of the Animal Ethics Committee of the First Affiliated Hospital of Shihezi University.