Research progress of quality control for the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Suan-Zao-Ren) and its proprietary Chinese medicines.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen Ziziphi Spinosae (SZS), the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow (Chinese name Suan-Zao-Ren), is widely distributed in China, Laos, Myanmar, and Iran. It is a classic traditional Chinese medicine with sedative and sleeping effects. In clinical practice, there are more than 155 proprietary Chinese medicines containing SZS. However, many commercial SZS products are difficult to qualify using current methods. Moreover, there is a scarcity of quality standards for SZS in proprietary Chinese medicines. AIM OF THE STUDY: The purpose of this study was to clearly reveal the quality indicators during the entire production process of SZS and its products. MATERIALS AND METHODS: This study reviewed more than 230 articles and related books on the quality control of SZS and its proprietary Chinese medicines published over the last 40 years (from January 1979 to October 2022). Moreover, where available, information on the quality of SZS and its proprietary Chinese medicines was also collected from websites for comparison, including online publications (e.g. PubMed, CNKI, Google Scholar, and Web of Science), the information at Yaozhi website and China Medical Information Platform, along with some classic books on Chinese herbal medicine. The literature and information search were conducted using keywords such as "Suan-Zao-Ren", " Ziziphus jujuba" and "quality control", and the latest results from various databases were combined to obtain valid information. The active components, which in vivo exposure, and Q-markers were also summarized. RESULTS: The jujuboside A, jujuboside B, and spinosin were revealed as the key Q-markers for SZS. Moreover, the advancements and prospects of the quality control for SZS and its extract, proprietary Chinese medicines, health foods, and adulterants were comprehensively summarized. The high-performance liquid chromatography-UV/evaporative light scattering detection and fingerprint analysis were found to be the mainstream methods for the SZS quality control. In particular, the novel quality evaluation method based on the unit content was applied for SZS and its proprietary Chinese medicines. Significant fluctuations were found in the contents of Q-markers. Moreover, the mass transfer rule of Q-markers was comprehensively clarified based on the entire production process, including production origins, ripening time, primary process, processing, compatibility decoction/extract, and storage. Ultimately, the crushing and compatibility of SZS were found to be the key steps affecting the active components. CONCLUSIONS: In short, this study provides solid evidences to reveal quality indicators for the entire production process of developing rational quality standards for SZS and its products. Moreover, this study also provides a template quality control overview, which could be extended to other traditional Chinese medicines.

Influence of JuA in evoking communication changes between the small intestines and brain tissues of rats and the GABAA and GABAB receptor transcription levels of hippocampal neurons.

ETHNOPHARMACOLOGICAL RELEVANCE: Jujuboside A (JuA) is a main active ingredient of semen ziziphi spinosae, which can significantly reduce spontaneous activity in mammals, increase the speed of falling asleep, prolong the sleeping time as well as improve the sleeping efficiency. In this study, the mechanism and the pathway of the sedative and hypnotic effect of JuA were investigated. MATERIALS AND METHODS: After being treated with JuA (in vitro), the rat׳s small intestine tissues cultures were used to stimulate the brain tissues. Then 27 cytokine levels were detected in the two kinds of tissue culture via liquid protein chip technology; In addition, the cultured hippocampal neurons of rat were treated with JuA, and γ-aminobutyric acid (GABA) receptor subunits (GABAAα1, GABAAα5, GABAAß1 and GABABR1) mRNAs were evaluated by Real-time PCR. RESULTS: The levels of IL-1α, MIP-1α, IL-1ß and IL-2 were reduced significantly after 3h of treating the small intestine tissues with JuA (200µl/ml), and the concentration change rates, in order, were -59.3%, -3.59%, -50.1% and -49.4%; these cytokines were transmitted to brain tissues 2h later, which could lead to significant levels of reduction of IL-1α, IFN-γ, IP-10 and TNF-α; the concentration change rates were -62.4%, -25.7%, -55.2% and -38.5%, respectively. Further, the intercellular communication network diagram was mapped out, which could suggest the mechanism and the pathway of the sedative and hypnotic effect of JuA. The results also indicated that JuA (50µl/ml) increased significantly GABAAα1 receptor mRNAs and reduced GABABR1, mRNAs in hippocampal neurons after 24h of stimulation; however, all the mRNA transcription levels of GABAAα1,GABAAα5, GABAAß1 and GABABR1 receptors increased significantly after 48h. CONCLUSION: JuA performed its specific sedative and hypnotic effect through not only adjusting GABA receptors subunit mRNAs expression, but also down-regulating the secretion of relevant inflammation cytokines on the intestinal mucosal system to affect the intercellular cytokine network between nerve cells in the brain. This mechanism is similar to that of melatonin.

HPLC-ELSD determination of triterpenoids and triterpenoid saponins in Ilex pupurea leaves.

AIM: To establish an HPLC-ELSD method for the quantification of pedunculoside, ziyuglycoside I and rutundic acid, in the leaves of Ilex purpurea Hassk. METHODS: By optimizing the chromatographic conditions of HPLC and the parameters of ELSD to study the methodology. Column: Allsphere ODS-2 (250 mm x 4.6 mm ID, 5 microns), mobile phase: methanol-water (59:41), flow rate: 1.0 mL.min-1, drift tube temperature: 59 degrees C, gas flow rate: 2.38 L.min-1. RESULTS: The calibration curves were linear in the range of 2.56-25.60 micrograms for pedunculoside, 1.64-16.40 micrograms for ziyuglycoside I and 3.74-37.40 micrograms for rutundic acid. The average recovery of pedunculoside was 96.3%, RSD 1.59% (n = 5), ziyuglycoside I 97.3%, RSD 3.82% (n = 5), rutundic acid 97.7%, RSD 2.11% (n = 5). All of RSDs of the precision were less than 4% (n = 6), and the reproduciblities less than 5% (n = 6). CONCLUSION: The method is simple, accurate, effective and feasible. It can be used for the determination of the contents of pedunculoside, ziyuglycoside I and rutundic acid in leaf of Ilex purpurea Hassk.