Advanced application of nanotechnology in active constituents of Traditional Chinese Medicines.

Traditional Chinese Medicines (TCMs) have been used for centuries for the treatment and management of various diseases. However, their effective delivery to targeted sites may be a major challenge due to their poor water solubility, low bioavailability, and potential toxicity. Nanocarriers, such as liposomes, polymeric nanoparticles, inorganic nanoparticles and organic/inorganic nanohybrids based on active constituents from TCMs have been extensively studied as a promising strategy to improve the delivery of active constituents from TCMs to achieve a higher therapeutic effect with fewer side effects compared to conventional formulations. This review summarizes the recent advances in nanocarrier-based delivery systems for various types of active constituents of TCMs, including terpenoids, polyphenols, alkaloids, flavonoids, and quinones, from different natural sources. This review covers the design and preparation of nanocarriers, their characterization, and in vitro/vivo evaluations. Additionally, this review highlights the challenges and opportunities in the field and suggests future directions for research. Nanocarrier-based delivery systems have shown great potential in improving the therapeutic efficacy of TCMs, and this review may serve as a comprehensive resource to researchers in this field.

Metabolic profile of danshen in rats by HPLC-LTQ-Orbitrap mass spectrometry.

Danshen, the dried root of Salvia miltiorrhiza Bunge (Lamiaceae), is one of the traditional Chinese medicines (TCMs) most commonly used for the treatment of cardiovascular and cerebrovascular diseases. However, little is known about the chemical and metabolic profiles of danshen in vitro or in vivo. In particular, more information is needed in relation to the 50% ethanol extracts usually used in danshen formulations such as Fufang Xueshuantong Capsules and Fufang Danshen tablets. High-performance liquid chromatography coupled with a linear ion trap-Orbitrap mass spectrometer (HPLC-LTQ-Orbitrap) provides a sensitive and accurate method for analyzing the composition of samples. This method was used to determine the in vitro and in vivo chemical and metabolic profiles of danshen. Sixty-nine components of danshen extract and 118 components of danshen in rat plasma, urine, feces, and bile were unambiguously or tentatively identified. These results not only revealed the material composition of danshen, but also provided a comprehensive research approach for the identification of multi-constituents in TCMs.

Effect of compatible herbs on the pharmacokinetics of effective components of Panax notoginseng in Fufang Xueshuantong Capsule.

Fufang Xueshuantong (FXT) is a well-known Chinese herbal formula which has been used to treat cardiovascular and ophthalmic diseases, especially diabetic retinopathy. Panax notoginseng (Burkill) F.H. Chen (PN) is the main herb of FXT, whose major bioactive constituents are ginsenosides. However, the scientific basis of the compatibility of FXT is still ambiguous. The present study investigated the scientific basis of the compatibility of FXT by comparing the pharmacokinetics of marker compounds after oral administrations of PN and FXT. A high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed for simultaneous detection of notoginsenoside R1 (NR1), ginsenoside Rg1 (GRg1), and ginsenoside Rb1 (GRb1) in rat plasma. The pharmacokinetic studies of FXT and PN were performed using the established method with the pharmacokinetic parameters being determined by non-compartmental analysis. The results showed that the pharmacokinetic parameters (maximum concentration, area under the curve (AUC0-t), clearance, and mean residence time) of NR1, GRg1, and GRb1 were significantly different after oral administration of FXT (P<0.05) compared with PN. The AUC0-t values of GRg1 and GRb1 were 1.7- and 3.4-fold greater, respectively, in FXT than in PN. The compatible herbs of FXT could prolong the retention time and increase the systemic exposure of NR1, GRg1, and GRb1 compared with PN in vivo, providing some scientific basis for the compatibility and clinical use of FXT.

[Distribution of chemical compounds of Fufang Xueshuantong capsule in eyes and kidney of beagle dogs].

Diabetic retinopathy(DR) and diabetic nephropathy(DN) are the most common complications of diabetes, and the main causes of death and disability of diabetes. Clinical reports showed that Fufang Xueshuantong capsule(FXT) had effective curative effect on DR and DN, but there was no report on the distribution of chemical compounds of FXT in beagle dog eyes and kidneys. In this study, FXT was given by gavage administration in Beagle dogs for 3 days, and then their eyeballs and kidneys were taken. The chemical compounds in beagle dog eyes and kidneys were detected by HPLC LTQ-Orbitrap technology. Furthermore, by comparing with the data from retrieving literature and references, the chemical compounds were identified by the accurate mass, retention time (tR), and MS/MS. Fourteen and 19 types of notoginsenosides were respectively identified in eyeballs and kidneys in this study, and these results could lay foundation for clarifying the effective ingredients of FXT in treatment of DR and DN.

[LC-LTQ-Orbitrap analysis on chemical constituents in Scrophulariae Radix extract and their metabolites in rat plasma].

Chemical constituents in extract of Scrophulariae Radix and their metabolites in rat plasma after oral administration were identified by HPLC-LTQ-Orbitrap. Samples were separated by a Venusil MP C18 column using a binary gradient elution. The information on the total ion chromatogram, the extraction chromatogram and the mass spectrogram in a negative mode were synthetically analyzed by comparing the retention time, MS and MS/MS spectra with literature data and some of reference standards to conduct a qualitative study on constituents of Radix Scrophulariae extract in vivo and in vitro. Totally 37 compounds from Scrophularia ningpoensis extract were detected including 12 iridoid glycosides, 20 phenylpropanoids and 5 unknown compounds. In vivo, harpagide, harpagoside and angoroside C were confirmed to enter into the blood in prototype forms. Besides, another 2 prototype compounds and 2 metabolites were detected in rat plasma after oral administration of S. ningpoensis extract. The results are beneficial for the determination of bioactive substances of S. ningpoensis and significant for further studies on S. ningpoensis.

[Phenanthrenes from aerial part of Juncus setchuensis with anxiolyticactivity].

Ten phenanthrenes, two organic acids, one organic acid ester and one flavonoid were isolated from the aerial part of Juncus setchuensis by various chromatographic techniques usingsilica gel, polyamide, Sephadex LH-20 as solid phases, and preparative HPLC. Their structures were identified by MS and NMR spectroscopic data as effusol(1), juncusol(2), juncuenin D(3), dehydroeffusol(4), dehydrojuncusol(5), juncuenin B(6),dehydrojuncuenin B(7), 2-methoxyl-7-hydroxyl-1-methyl-5-vinyl phenanthrene(8), 2-hydroxyl-7-carboxy-1-methyl-5-vinyl-9,10-dihydrophenanthrene(9), 2-hydroxyl-7-carboxyl-1-methyl-5-vinylphenanthrene(10), luteolin(11), vanillic acid(12), daphnetin(13), p-coumaric acid(14), respectively. Compound 13 was isolated from the genus Juncus for the first time and compounds 5, 8-12 were isolated from J. setchuensis for the first time. The elevated plus-maze(EPM) was used to evaluate the anxiolytic activity of compounds 6 and 7. Compound 6 at 5 mg•kg⁻¹ and 10 mg•kg⁻¹ showed anxiolytic activity as well as compound 7 at 10 mg•kg⁻¹ and 20 mg•kg⁻¹.

Analysis of main constituents and mechanisms underlying antidepressant-like effects of Xiaochaihutang in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT), a famous Chinese herbal formula which consists of seven Chinese herbs, has been used clinically in depressive disorders in China. Our previous studies have demonstrated that XCHT improved depressive-like behavior in several animal models of depression. However, therapeutic basis of XCHT on depression are challenging, due to the complex active constituents of XCHT and the unclear pharmacological mechanism of action. MATERIALS AND METHODS: To provide further insights into therapeutic basis of XCHT, the core in compatibility of XCHT on antidepressant therapy was assessed by the method of orthogonal array design. The comparative evaluations on antidepressant effects of XCHT and its core in compatibility were executed by tail suspension test (TST), forced swim test (FST), novelty suppressed feeding test (NSFT), reserpine-induced hypothermia and palpebral ptosis. Moreover, the potential mechanism was explored by investigating levels of monoamine neurotransmitters in hypothalamus and striatum and neurogenesis in hippocampus. Chemical profile of active constituents in plasma after oral administration of the core in compatibility of XCHT was revealed by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: The results of orthogonal array design experiment showed that Huangqin (Radix scutellariae), Renshen (Ginseng) and Gancao (Radix glycyrrhizae), defined as HRG, might be the core in compatibility of XCHT on antidepressant therapy. In accordance with XCHT, oral administration of HRG for 15 days significantly reduced immobility duration in TST and FST without affecting locomotor activity. Both HRG and XCHT increased immobility latency in FST, decreased the latency in NSFT, reversed reserpine-induced hypothermia and palpebral ptosis. Moreover, both HRG and XCHT significantly increased levels of 5-HT and DA in hypothalamus. In addition, HRG could remarkably increase Ki-67 and doublecortin (DCX) positive cells in hippocampus. A total 25 active constituents in plasma, including 14 prototype components and 11 metabolites, were identified by UPLC-MS/MS after oral administration of HRG. CONCLUSION: The present results reveal that HRG is supposed to be the core in compatibility of XCHT on antidepressant therapy. In accordance with XCHT, HRG exerts significant antidepressant-like effects, which are likely attributed to regulating serotonergic and dopaminergic systems and increasing hippocampal neurogenesis. The constituents identified in plasma after oral administration of HRG may be the potential active ingredients for the treatment of depression.

[Construction of universal quantitative models for determination of cefoperazone sodium for injection from different manufacturers using near infrared reflectance spectroscopy].

Universal quantitative models using NIR reflectance spectroscopy in two different kinds of sampling mode were developed for the analysis of cefoperazone sodium for injection from different manufacturers in China. The quantitative models were established using partial least squares(PLS). Nineteen batches of cefoperazone sodium for injection samples from 9 different manufacturers were predicted by the quantitative models. The root mean square errors of cross validation (RMSECV) and the root mean square errors of prediction (RMSEP) of the model in integrating sphere sampling mode were 0. 99 and 0. 98, respectively. The values of RMSECV and RMSEP of the model in fibre sampling mode were 1. 12 and 1. 17, respectively. Based on the ICH guidelines and characteristics of NIR spectra, the quantitative models were then evaluated in terms of specificity, linearity, accuracy, and precision. The authors' study has shown that it is feasible to build a universal quantitative model in fibre sampling mode for quick analysis of pharmaceutical products from different manufacturers. As a result of its good specificity and applicability, the model could be used for quick, non-destructive prescreening of counterfeit and substandard drugs in the mobile vehicle.