[Health risk assessment of exogenous harmful pollutants in Chinese medicine: a review].

In recent years, the quality and safety problems have been limiting the internationalization of Chinese medicine. The pollutants in Chinese medicine, particularly the exogenous harmful pollutants mainly including mycotoxins, pesticide residues, heavy metals, harmful elements, and sulfur dioxide, are of high risks for people. Therefore, the World Health Organization(WHO) and relevant national organizations have clearly defined the maximum residue limits(MRLs) of such pollutants. Chinese Pharmacopoeia(2020 edition, volume Ⅳ) also demonstrates the detection methods, MRLs and preliminary risk assessment methods for four typical exogenous harmful pollutants in Chinese medicine. Therefore, continuous optimization of the health risk assessment system can further help further raise the quality and safety of Chinese medicine. This paper reviews the research on the health risk assessment of four typical exogenous harmful pollutants in Chinese medicine and discusses the problems of and challenges for the assessment system, which is expected to lay a scientific basis for the establishment of the risk warning mode and response measures suitable for specific types of Chinese medicine.

[Simultaneous determination of 8 main compounds in Eclipta Herba by UPLC].

To establish an UPLC method for the simultaneous determination of 8 compounds in Eclipta Herba, such as isoquercitrin, luteoloside, demethylwedelolactone, isochlorogenic acid A, isochlorogenic acid C, luteolin, wedelolactone and apigenin. The experiment was performed with a Waters Acquity UPLC BEH C18 (2.1 mm×100 mm, 1.7 µm) column by gradient elution of 0.1% formic acid in water and acetonitrile: 0-4 min,10%-13% A; 4-10 min, 13%-16% A; 10-13 min, 16%-25% A; 13-17 min, 25%-28% A; 17-20 min,28%-40% A;20-25 min,40%-95% A. The flow rate was 0.3 mL•min⁻¹.. The condition of was the colum temperature was maintained at 35 ℃ and the detected wavelength was set at 350 mm. 8 components were separated clearly by this method. Also a good linearity was obtained between the chosen concentration(r≥0.999 0). The measured data showed that the recovery rate range from 96.60%-103.4% (n=6) and their RSD values were 0.86%-2.4%. The method has high recovery rate, good reproducibility and stability. It provides a scientific basis for the identification and quality evaluation of Eclipta Herba.

Multielemental composition of suet oil based on quantification by ultrawave/ICP-MS coupled with chemometric analysis.

Suet oil (SO) has been used commonly for food and medicine preparation. The determination of its elemental composition has became an important challenge for human safety and health owing to its possible contents of heavy metals or other elements. In this study, ultrawave single reaction chamber microwave digestion (Ultrawave) and inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to determine 14 elements (Pb, As, Hg, Cd, Fe, Cu, Mn, Ti, Ni, V, Sr, Na, Ka and Ca) in SO samples. Furthermore, the multielemental content of 18 SO samples, which represented three different sources in China: Qinghai, Anhui and Jiangsu, were evaluated and compared. The optimal ultrawave digestion conditions, namely, the optimal time (35 min), temperature (210 °C) and pressure (90 bar), were screened by Box-Behnken design (BBD). Eighteen samples were successfully classified into three groups by principal component analysis (PCA) according to the contents of 14 elements. The results showed that all SO samples were rich in elements, but with significant differences corresponding to different origins. The outliers and majority of SO could be discriminated by PCA according to the multielemental content profile. The results highlighted that the element distribution was associated with the origins of SO samples. The proposed ultrawave digestion system was quite efficient and convenient, which could be mainly attributed to its high pressure and special high-throughput for the sample digestion procedure. Our established method could be useful for the quality control and standardization of elements in SO samples and products.

[Research thoughts and technology system framework of jinfukang oral liquid secondary exploitation].

Most Chinese medicine has good clinical efficacy and application. However, the material basis is vague for the lack of basic research, the value of Chinese medicine is hard to reflect for the low technology level and product quality is difficult to maintain for the quality control indicator selection is incorrect. Chinese medicine Jinfukang oral liquid is a typical product of Chinese medicines. Jinfukang oral liquid was selected as a model drug in this article. Based on the overall concept and systems theory of traditional Chinese medicine, the research idea and technology system for modern Chinese medicine secondary exploitation was formed. The system includes three parts, for the first, basic research to make clear the components structure and their action mechanism, for the second, technology upgraded to optimize process and improve the product quality, for the last, exploring the associated industry to form the industrial chain. The research ideas and technology system based on the material basis research and development of modern Chinese medicine, guided with component structure in Chinese medicine and aimed clinical needs. This research ideas and technology system provides strategies and methods for the development of modern Chinese medicine secondary exploitation.

[Comparison of protective effects of eight ethyl acetate extracts from Eclipta prostrate on NHBE cells based on component structure theory].

To analyze and compare the protective effects of active components in different ethyl acetate extracts (EAEEPs) from Eclipta prostrate, in order to study the comparison of materials bases protecting normal human bronchial epithelial (NHBE) cells. The MTT assay was taken to compare the protective effect of different EAEEPs on cigarette smoke extracts (CSE) -induced NHBE cells. The ultra-performance liquid chromatography (UPLC) was applied to analyze the content of phenolic acid, coumaric grass ether and flavonoid in EAEEPs. According to the results, all of the eight EAEEPs (0-200 mg x L(-1)) showed certain protective effect on NHBE cells, with statistical difference. Specifically, the total mass of EAEEP VII (89.15 mg x L(-1)) and EAEEP VIII (57.44 mg x L(-1)), which showed the strongest activity, was not the highest, while EAEEP III (132.25 mg x L(-1)) displayed the highest total mass. In the combination with the "component structure" theory, the analysis showed a significant difference in the mass structure among phenolic acid, coumaric grass ether and flavonoid in EAEEP VIII and EAEEP VIII, which were 1.0: 1. 0: 0.5 and 1.0: 1.9: 0.8, respectively. The results suggested a specific optimal "component structure" relationship may exist in EAEEP, which could provide reference for the material base study and quality control.

[Efficacy of a Daltuzumab-containing Regimen in Patients with mSMART High-Risk Multiple Myeloma].

OBJECTIVE: To investigate the efficacy and safety of a treatment regimen based on daratumumab in patients with high-risk relapsed refractory multiple myeloma(MM) with mSMART 3.0 score. METHODS: Clinical data were collected from 16 patients with mSMART3.0 score high-risk relapsed refractory MM treated at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from May 2020 to May 2023, all of whom received daltezumab-based regimen (regimen drugs including dexamethasone, isazomib, bortezomib, lenalidomide). The efficacy and safety of the treatment were retrospectively analyzed. RESULTS: The median age of 16 patients was 63.5 (47-70) years old, including 10 cases of IgG type, 2 cases of IgA type, and 4 cases of light chain type. The curative efficacy was judged in all 16 patients, with an overall response rate of 93.75% (15/16), including 4 cases of strict complete remission (sCR), 1 case of complete remission (CR), 2 case of very good partial remission (VGPR), partial remission (PR) in 5 cases, and minor remission (MR) in 3 cases. The median follow-up time was 11(2-30) months, and the median progression-free survival and median overall survival were not achieved in 16 patients at the median follow-up period. The hematologic adverse effects of the treatment regimen using daratumumab-based were mainly neutropenia, and the non-hematologic adverse effects were mainly infusion-related adverse reactions and infections. CONCLUSION: Daratumumab-based regimen for the treatment of relapsed refractory MM patients with high risk of mSMART3.0 score has better efficacy and safety.

[Chemical constituents of Nauclea officinalis].

In order to study the chemical constituents in the water extract of the stem of Nauclea officinalis, column chromatography over D101 macroporous resin and silica gel and an automatic purification system were used to isolate and purify the chemical constituents from the extract. Nine compounds were obtained. By analysis of the physicochemical properties and spectral data, their structures were identified as naucleamide G (1), 3, 4-dimethoxyphenol-beta-D-apiofuranosyl (1-->6)-beta-D-glucopyranoside (2), kelampayoside A (3), 3alpha, 5alpha-tetrahydrodeoxycordifoline lactam (4), naucleamide A-10-O-beta-D-glucopyranoside (5), pumiloside (6), 3-epi-pumiloside (7), strictosamide (8) and vincosamide (9), separately. Among them, compound 1 is a new compound, compound 2 was found in plants of the genus Nauclea for the first time, and compounds 3 and 4 were isolated from this plant for the first time.

3-(tert-But-oxy-carbon-yl)-2-(4-chloro-phen-yl)-1,3-thia-zolidine-4-carb-oxy-lic acid.

In the title compound, C(15)H(18)ClNO(4)S, the thia-zolidine ring adopts a twisted conformation about the S-C(methyl-ene) bond. The dihedral angle between the five- and six-membered rings is 77.2 (3)°. In the crystal, the mol-ecules are linked by O-H⋯O hydrogen bonds, generating C(7) chains propagating in [100].

Wedelolactone-Loaded Micelles Ameliorate Doxorubicin-Induced Oxidative Injury in Podocytes by Improving Permeability and Bioavailability.

Wedelolactone (WED) is commonly used for the treatment of doxorubicin (DOX)-induced kidney damage, but its efficacy is limited by its poor solubility and bioavailability. In this study, we developed a novel delivery system of WED-loaded micelles (WED-M) with Solutol® HS15 and lecithin at an optimized ratio of 7:3 to improve the poor permeability and bioavailability of WED and to enhance its efficacy. The spherically shaped WED-M (particle size: 160.5 ± 3.4 nm; zeta potential: -30.1 ± 0.9 mV; entrapment efficiency: 94.41 ± 1.64%; drug loading: 8.58 ± 0.25%; solubility: 1.89 ± 0.06 mg/ml) has continuous stability over 14 days and a sustained release profile. The permeability of WED-M in Caco-2 cells indicated a significant 1.61-fold higher Papp AP to BL ratio than WED alone. Additionally, pharmacokinetic evaluation of WED-M demonstrated that the bioavailability of WED was increased 2.78-fold. Both HE staining and transmission electron microscopy showed an obvious improvement of pathological damage in WED-M treatment. Moreover, WED-M significantly enhanced the ROS level in mice and MPC5 podocytes. We concluded that using this micelle delivery system for WED could improve its permeability and bioavailability to attenuate DOX-induced oxidative injury in podocytes. This study provided important information on the fact that the micelle delivery system, WED-M, showed a significant improvement of renal damage.

[Effects of Arsenic Trioxide on Cdc20 and Mad2 in Acute Myeloid Leukemia HL-60 Cell Line].

OBJECTIVE: To investigate the effects of arsenic trioxide (As2O3) on Cdc20 and Mad2 in process of AML HL-60 cell proliferation. METHODS: The proliferation of HL-60 cells was detected by CCK-8 method at different concentrations of arsenic trioxide for 24, 48 and 72 hours. The cell morphological changes were observed by inverted microscopy. The expressions of Mad2 and Cdc20 mRNA and protein in HL-60 cells treated with As2O3 for 48 h were detected by real-time PCR and Western blot respectively. RESULTS: Arsenic trioxide significantly inhibited the HL-60 cell proliferation and displayed a good time-dose correlation. RT-PCR and Western blot showed that the expression of Mad2 was up-regulated and the expression of Cdc20 was down-regulated in HL-60 cells treated with arsenic trioxide of different concentration (4,8,10 µmol/L). CONCLUSION: Arsenic trioxide can inhibit the human acute myeloid leukemia HL-60 cell proliferation, and its mechanism may be related with up-regulation of Mad2 expression and down-regulation of Cdc20 expression.

Enhanced bioavailability of apigenin via preparation of a carbon nanopowder solid dispersion.

In this study, a novel carbon nanopowder (CNP) drug carrier was developed to improve the oral bioavailability of apigenin (AP). Solid dispersions (SDs) of AP with CNP were prepared, and their in vitro drug release and in vivo performance were evaluated. The physicochemical properties of the formulations were examined by differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. Drug release profiles showed that AP dissolution from the CNP-AP system (weight ratio, 6:1) after 60 minutes improved by 275% compared with that of pure AP. Moreover, the pharmacokinetic analysis of SD formulations in rats showed that the AP area under the curve0-t value was 1.83 times higher for the CNP-AP system than for pure AP, indicating that its bioavailability was significantly improved. In addition, compared with pure AP, SDs had a significantly higher peak and shorter time to peak. Preliminary intestinal toxicity tests indicated that there was no significant difference in the tissues of the rats treated with the CNP-AP system, rats treated with the CNP alone, and controls. In conclusion, CNP-based SDs could be used for enhancing the bioavailability of poorly water-soluble drugs while also improving drug safety.

New metabolite profiles of Danshensu in rats by ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry.

In our research, ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (U-HPLC/Q-TOF-MS) was established for analyzing the metabolite profiles of Danshensu (DSS) in rat feces, bile, urine, plasma and the possible metabolic pathways were subsequently proposed after the oral dose of 80mg/kg; rat biological samples were collected and pretreated by protein precipitation. Then, the samples were injected into an Acquity ultraperformance liquid chromatography BEHC column with mobile phase consisted of acetonitrile (solvent A)-0.1% formic acid-water (solvent B) with a linear gradient elution program. Totally, 17 metabolites of DSS were identified, including 4, 5, 4 and 4 metabolites in the feces, urine, blood, and bile samples respectively. Most of them were to our knowledge reported for the first time. The results indicated that DSS was metabolized via dehydrogenation, deoxygenation, methylation, glucuronidation, and sulfation pathways in vivo. Among these, methylation was considered as the main physiologic processes of it. This study revealed that U-HPLC/Q-TOF-MS was more accurate and sensitive to detect and identify the possible metabolites and to better understand the metabolism of DSS in vivo.

Protection of glycyrrhizic acid against AGEs-induced endothelial dysfunction through inhibiting RAGE/NF-κB pathway activation in human umbilical vein endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Licorice (Glycyrrhiza uralensis roots) is used as a traditional medicine for the treatment of diabetes mellitus and its vascular complications. Glycyrrhizic acid (GA, also known as Glycyrrhizin), a triterpenoid saponin glycoside, is considered to be a bioactive component in Licorice and is beneficial to diabetic vascular complications. AIM OF STUDY: The present study was conducted to evaluate the potential protective activities on AGEs-induced endothelial dysfunction, including anti-apoptosis, antioxidant stress and anti-proinflammatory responses, and explore the underlying mechanism. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were incubated and pre-treated with GA (10(-9)-10(-6)M) or RAGE-Ab (5µg/ml) in the presence or absence of 200µg/ml AGEs. AO/EB fluorescence staining assay was performed to evaluate anti-apoptosis activity. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in cell supernatant were detected by kits while the intracellular reactive oxygen species (ROS) generation was determined by 2,7-dichlorodihydrofluorescin diacetate (DCFH-DA) kit. Immunocytochemistry analysis was designed to determine transforming growth factor beta1(TGF-ß1) protein expression while immunofluorescence analysis for RAGE and NF-kB. The protein expressions of TGF-ß1, RAGE and NF-kB were analyzed by Western blot analysis. RESULTS: Pretreatment with GA at a concentration of 10(-8)-10(-6)M significantly reduced the AGEs-induced apoptosis in HUVECs. GA significantly increased antioxidant enzyme SOD activity and decreased peroxide degradation product MDA level in a dose-dependent manner. Furthermore, GA also remarkably inhibited the overgeneration of AGEs-induced ROS. Both immunocytochemistry analysis and western blot analysis showed that GA significantly decreased the protein expression of poinflammatory cytokine TGF-ß1 in a similar manner which RAGE-Ab did. Additionally, AGEs-induced RAGE and NF-kB protein expressions were down-regulated significantly by the pretreatment with GA or RAGE-Ab. CONCLUSION: These findings provide evidences that GA possesses protective activity on AGEs-induced endothelial dysfunction, including anti-apoptosis, anti-inflammation and antioxidant stress, via inhibiting RAGE/NF-kB pathway. GA might be an alternative for the prevention and treatment of diabetic vascular complications in an appropriate dosage.