Colorimetric-SERS dual-mode sensing of Pb(II) ions in traditional Chinese medicine samples based on carbon dots-capped gold nanoparticles as nanozyme.

Peroxidase (POD)-mimicking nanozymes have got great progress in the sensing field, but most nanozyme assaying systems are built with a single-signal output mode, which is vulnerable to the effect of different factors. Thus, establishment of a dual-signal output mode is necessary for acquiring dependable and durable performance. This work described an Fe doped noradrenaline-based carbon dots and Prussian blue (Fe,NA-CDs/PB) nanocomposite as a POD-like nanozyme and modified gold nanoparticles (AuNPs) for the colorimetric and surface-enhanced Raman scattering (SERS) dual-mode sensor of Pb(II) in traditional Chinese medicine samples. With 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 3,3',5,5'-tetramethylbenzidine (TMB) as the substrates, it was found that the addition of Pb(II) inhibited the POD-like activity of Fe,NA-CDs/PB and AuNPs, so it was used for colorimetric and SERS dual-mode assays. The POD-like activity was shown to be a "ping-pong" catalytic mechanism, whereas the addition of Pb(II) produced noncompetitive inhibition with modulatory effects on Fe,NA-CDs/PB. The linear response range for colorimetric and SERS sensor detection of Pb(II) was 0.01-1.00 mg/L with the detection limit of 5 µg/L and 8 µg/L, respectively. This dual-mode detection system shows excellent selectivity. More importantly, the Pb(II) in traditional Chinese medicine samples have successfully assayed with good recovery from 90.4 to 108.9 %.

Improvement of the Thermal Stability and Aqueous Solubility of Three Matrine Salts Assembled by the Similar Structure Salt Formers.

Matrine (MAT), a natural Chinese herbal medicine, has a unique advantage in the treatment of various chronic diseases. However, its low melting point, low bioavailability, and high dosage restrict its subsequent development into new drugs. In this study, three kinds of MAT salts, namely, MAT-2,5-dihydroxybenzoic acid (MAT-25DHB), MAT-2,6-dihydroxybenzoic acid (MAT-26DHB), and MAT-salicylic acid-hydrate (MAT-SAL-H2O), were designed and synthesized to improve the drugability of MAT. The three salts were characterized by using various analytical techniques, including single-crystal X-ray diffractometry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetry, and infrared spectroscopy. The results of the thermal stability evaluation showed that the formation of salts improved the stability of MAT; MAT-25DHB is the most stable salt reported at present. The results of aqueous solubility showed that the solubility of MAT-25DHB was higher than that of MAT, while that of MAT-26DHB and MAT-SAL-H2O were less. Given that the MAT-25DHB salt further improved the solubility of MAT, it is expected to be subjected to further research as an optimized salt. Lattice energy and solvation free energy are important factors affecting the solubility of salts; the reasons for the changes of solubility and stability of three kinds of salts are explained by calculating them.

The Traditional Mongolian Medicine Qiqirigan-8 Effects on Lipid Metabolism and Inflammation in Obesity: Pharmacodynamic Evaluation and Relevant Metabolites.

Objective: Traditional Mongolian Medicine Qiqirigan-8 (MMQ-8) is a Chinese botanical drug with effective pharmacological properties in obesity. However, the pharmacological mechanism of MMQ-8 remains unclear. This study aimed to determine the active metabolites of MMQ-8 and its therapeutic effects on lipid metabolism and inflammation. Methods: The active metabolites of MMQ-8 were identified by ultrahigh-performance liquid chromatograph Q extractive mass spectrometry (UHPLC-QE-MS) assay and network analysis. An obesity rat model induced by high-fat diet was used in the study. Serum levels of lipids and inflammatory factors were detected using biochemical analysis and enzyme-linked immunosorbent assay (ELISA). Pathological analysis of liver tissues and arteries was conducted with hematoxylin and eosin (H&E) staining and immunohistochemistry. Protein expression of the tumor necrosis factor (TNF) signaling pathway was investigated by Western-blot. Simultaneously, bone marrow cells were used for RNA sequencing and relevant results were validated by cell culture and quantitative real-time polymerase chain reaction (RT-qPCR). Results: We identified 69 active metabolites and 551 target genes of MMQ-8. Of these, there are 65 active metabolites and 225 target genes closely related to obesity and inflammation. In vivo, we observed that MMQ-8 had general decreasing effects on body weight, white adipose tissue weight, and serum lipids. MMQ-8 treatment notably decreased the liver function markers and hepatic steatosis, and significantly decreased inflammation. In serum, it notably decreased TNF-α, interleukin (IL)-6, and inducible nitric oxide synthase (INOS), while elevating IL-10 levels. MMQ-8 treatment also significantly inhibited proteins phosphorylation of nuclear factor-kappa B inhibitor alpha (IκBα), mitogen-activated protein kinase (p38), extracellular regulated kinase 1/2(ERK1/2), and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and decreased vascular endothelium damage and macrophage infiltration and polarization to M1. These findings coincide with the RNA-sequencing data of bone marrow cells and results of in vitro experiments. Conclusion: We determined the pharmacological actions and relevant metabolites of MMQ-8 in obesity for the first time. Our study revealed MMQ-8 can optimize lipid metabolism and reduce chronic inflammation in obesity. However, more in-depth research is needed, for example, to understand the principle of compound compatibility and the inhibition effects on hepatic steatosis, T cell differentiation, and inflammatory signal transduction.

Insights Into the Properties of Amygdalin Solvatomorphs: X-ray Structures, Intermolecular Interactions, and Transformations.

Amygdalin is an effective component of the traditional Chinese medicine bitter almond, peach kernel, and plum kernel. It has pharmacological effects, such as relieving cough and asthma. In a study of the crystallization process, we found a series of solvatomorphs of amygdalin (including hydrate). Interestingly, in the structures of these solvatomorphs, the same characteristic structural fragment is present, that is, amygdalin dihydrate. Multiple analytical techniques were used to characterize the solvatomorphs, such as X-ray diffraction and thermogravimetry-mass spectrometry. Void calculations of water and solvent were used to analyze the occupied volume in the unit cell of the corresponding solvatomorphs to explain the formation mechanism of the solvatomorphs from the perspective of space. To elucidate the formation mechanism of the solvatomorphs with this kind of characteristic structure from the perspective of energy, theoretical calculations based on density functional theory were applied, such as energy decomposition and molecular electrostatic potential surfaces. In addition, the transformation phenomenon between these solvatomorphs and amygdalin was identified, and the transformation pathways are described in detail.

TPGS-Modified Long-Circulating Liposomes Loading Ziyuglycoside I for Enhanced Therapy of Myelosuppression.

BACKGROUND: Ziyuglycoside I (ZgI), an active ingredient isolated from traditional Chinese medicine Sanguisorba officinalis L, has been demonstrated to increase the leucocytes and protect hematopoietic stem cells. However, the poor solubility and a short half-life of ZgI limit its bioavailability and efficacy. The D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) has been widely used to increase the solubility, improve the encapsulation rate, and extend the half-life of drugs. METHODS: Here, we formulated the TPGS-modified long-circulating liposomes loading ZgI with a sustained drug release and enhanced therapy for myelosuppression. ZgI-TPGS-liposomes were manufactured using a thin-film hydration technique, followed by characterizations of physicochemical properties, including the particle size, zeta potential, TEM, SEM, FTIR, XRD, stability, drug loading (DL), encapsulation efficiency (EE). The in vitro and in vivo delivery efficiency were further evaluated by cellular uptake, in vitro drug release and in vivo pharmacokinetics. Finally, therapeutic effect on myelosuppression was investigated. RESULTS: The ZgI-TPGS-liposomes had an particle size of 97.89 ± 1.42 nm and ZP of -28.65 ± 0.16 mV. It exhibited DL of 9.06 ± 0.76% and EE of 92.34 ± 3.83%, along with excellent storage stability, cellular uptake and sustained drug release to free ZgI and liposomes without TPGS. Additionally, the TPGS modified liposomes significantly enhanced the therapeutic effect of ZgI on CTX induced myelosuppression, which can be confirmed in the apoptosis inhibition and cell viability promotion of CTX injured HSPC-1 cells. Also, the mice in vivo pharmacodynamics demonstrated that TPGS liposomes promoted ZgI increasing the numbers of leucocytes and neutrophils in myelosuppression mice induced by CTX. CONCLUSION: Our research suggest that TPGS-modified long-circulating liposomes loading ziyuglycoside I has potential application in myelosuppression therapy.

The comprehensive study on the therapeutic effects of baicalein for the treatment of COVID-19 in vivo and in vitro.

Baicalein is the main active compound of Scutellaria baicalensis Georgi, a medicinal herb with multiple pharmacological activities, including the broad anti-virus effects. In this paper, the preclinical study of baicalein on the treatment of COVID-19 was performed. Results showed that baicalein inhibited cell damage induced by SARS-CoV-2 and improved the morphology of Vero E6 cells at a concentration of 0.1 µM and above. The effective concentration could be reached after oral administration of 200 mg/kg crystal form ß of baicalein in rats. Furthermore, baicalein significantly inhibited the body weight loss, the replication of the virus, and relieved the lesions of lung tissue in hACE2 transgenic mice infected with SARS-CoV-2. In LPS-induced acute lung injury of mice, baicalein improved the respiratory function, inhibited inflammatory cell infiltration in the lung, and decreased the levels of IL-1ß and TNF-α in serum. In conclusion, oral administration of crystal form ß of baicalein could reach its effective concentration against SARS-CoV-2. Baicalein could inhibit SARS-CoV-2-induced injury both in vitro and in vivo. Therefore, baicalein might be a promising therapeutic drug for the treatment of COVID-19.

Highly photoluminescent N, P doped carbon quantum dots as a fluorescent sensor for the detection of dopamine and temperature.

In recent times, fluorescent carbon quantum dots (CQDs) as an optical sensor have attained massive attention owing to their excellent optical properties. In current investigation, our group presented an easy and economical methodology to synthesize the nitrogen and phosphorous doped carbon quantum dots (N, P doped CQDs) for sensing dopamine (DA) and temperature in aqueous medium. The synthesized CQDs were characterized by using XRD, XPS, TEM, UV-Vis, FT-IR and fluorescence techniques. The N, P doped CQDs were synthesized via one-step microwave digestion method by using citric acid, ethylenediamine and urea phosphate as precursors. This method established the noble water solubility, good optical performances and fluorescence thermosensitivity of N, P doped CQDs. Also, N, P doped CQDs demonstrated a wide linear range of 10-500 µM (R2 = 0.994) and offered an electrifying detection limit of 0.021 µM for quantifying the dopamine. Moreover, this sensor possessed a good sensitivity, reversibility and linearity in the range of 10-70 °C. In addition, the CQDs sensing system repel the interference from probable foreign substances in real sample analysis, and attained good recoveries, which revealed the tremendous selectivity and adequate accuracy of the carbon quantum dots for sensing dopamine. The proposed N, P doped CQDs are simple as well as effective optical nanosensor and clasps venerable potential to widen the applications in analysis of biomolecules and other areas.

[Polymorphism of shikimic acid].

This study was performed to systematically investigate the polymorphism of shikimic acid. Through optimizing the recrystallization solvent, solvent volume, recrystallization temperature, time and pressure, three crystal forms were discovered and prepared. The differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray powder diffraction (PXRD) and infrared spectrometry (IR) were used to characterize these solid states. Furthermore, the influencing factor experiments were used to explore the stability of these polymorphisms and the transformation among them. Three new polymorphisms were prepared and identified. The results indicated that only PXRD could identify different polymorphisms and there was no solvent in all three crystal forms. The composition, thermodynamic property and transformation of these crystal forms were described in this work. Furthermore, an effective method for qualitative analysis of these crystal forms was established.

Certification of a new certified reference material of honokiol.

Honokiol is the most important active pharmaceutical ingredient in Magnolia officinalis, which is a famous traditional Chinese medicine and commonly used in clinical practice. In order to control the quality of honokiol and related pharmaceuticals, a new certified reference material (CRM) of honokiol was developed. The studies of sample preparation, homogeneity, stability, value assignment, and uncertainty evaluation were accomplished in this paper. Three different methods, including differential scanning calorimetry (DSC), mass balance method (MB), and coulometric titration (CT), were employed to determine the purity of honokiol. Specifically, the DSC and CT methods for purity determination of honokiol were established for the first time. The purity of honokiol CRM, after validation and evaluation, was found to be 99.3%, with an expanded uncertainty of 0.5% (k = 2).

Development of new reference material neohesperidin for quality control of dietary supplements.

BACKGROUND: Neohesperidin is an important natural flavanone glycoside distributed in several citrus species. This compound is widely used as a raw material for food additives in the food industry. The request for certified reference materials (CRMs) in dietary supplements was stipulated by the National Administrative Committee for CRMs and was underpinned by the need to improve the accuracy and comparability of measurement data and to establish metrological traceability of analytical results. RESULTS: This paper reports the sample preparation methodology, homogeneity and stability studies, value assignment and uncertainty estimation of a new certified reference material of neohesperidin (GBW09522). Differential scanning calorimetry, coulometric titration and mass balance methods proved to be sufficiently reliable and accurate for certification purposes. The certified value of neohesperidin CRM is 994 g kg(-1) with an expanded uncertainty of 4 g kg(-1) (k = 2). The reference material described above was homogeneous and stable for 12 months at a storage temperature of 25 °C. CONCLUSION: The new CRM of neohesperidin can be used to validate analytical methods and improve the accuracy of measurement data as well as quality control of neohesperidin-related dietary supplements, foods, traditional herbs and pharmaceutical formulations.

[Research on determination of chemical purity of andrographolide by coulometric titration method].

The determination of chemical purity of andrographolide by coulometric titration method is studied in this paper. The coulometric titration was carried out in a mixture composed of 4 mol x L(-1) hydrochloric acid and 1 mol x L(-1) potassium bromide solution and 1 mol x L(-1) potassium nitrate solution (1:1). Bromine is electrogenerated at the anode and reacts with the andrographolide. The number of electrons involved in the eleatrode reaction is 2. Purity of andrographolide is 99.76% compared with 99.77% utilizing area normalization method by HPLC. The RSD are 0.33% and 0.02% respectively. The results from two methods are consistent, so the determination of chemical purity of andrographolide by coulometric titration method is scientific and feasible. The method is rapid, simple, convenient, sensitive and accurate. The reference material is not essential in the method. The method is suitable for determination of chemical purity of andrographolide.

[Experimental study on the effect of Glycyrrhiza on small intestinal motility in rats].

AIM: To investigate the effects of glycyrrhiza decoction on migrating myoelectric complex (MMC) and gastrointestinal hormone in small intestine in rats. METHODS: We observed MMC cycle,phase Ill duration,fast wave numbers of phase III of MMC in one minute, fast wave numbers of one cluster in phase III of MMC of small intestine of glycyrrhiza group and control group rats with electrophysiology method, and immunohistochemistry to examine relative content of serotonin (5-HT), substance p(SP) and vasoactive intestinal polypeptide (VIP) in small intestinal chromophil (EC) and myenteric nerve plexus in small intestine of control group and glycyrrhiza group rats. RESULTS: Compared glycyrrhiza group with control group,we found that glycyrrhiza was able to decrease fast wave numbers in one minute and fast wave numbers in one cluster in phase III of MMC of small intestine (P < 0.05), and evidently extend small intestinal cycle of MMC (P < 0.05), it also shortened the phase III III duration (P < 0.05) or made the phase III of MMC absent. Compared glycyrrhiza group with control group it was indicated that content of 5-HT in small intestinal mucous membrane and myenteric nerve plexus was evidently decreased (P < 0.05), and content of SP in myenteric nerve plexus of small intestine of rats was evidently decreased (P < 0.05), and content of VIP in small intestine of rats was evidently increased (P < 0.05). CONCLUSION: Glycyrrhiza is able to inhibit small intestinal motility, this inhibition is related with the amount of 5-HT, SP, VIP secreted by small intestinal mucous membrane of rats.