Jujubae Fructus extract prolongs lifespan and improves stress tolerance in Caenorhabditis elegans dependent on DAF-16/SOD-3.

Jujubae Fructus, the fruit of Ziziphus jujuba Mill has been used as one of the medicine food homology species for thousands of years in China. Studies have shown that the active ingredients of Jujubae Fructus have a variety of biological effects, but its role in the aging process still lacks knowledge. Here, we investigated the effect of Jujubae Fructus extract (JE) on Caenorhabditis elegans lifespan and its potential mechanism. The lifespan of C. elegans treated with JE was signifificantly increased in a dose-dependent manner. In addition, JE treatment prolonged the reproductive period and increased normal activity during aging in C. elegans. Similarly, JE supplementation also enhanced the resistance to heat and oxidative stress in C. elegans. Furthermore, the mutant worms' lifespan assays demonstrated that JE requires daf-16 to prolong lifespan. DAF-16::GFP analysis of TJ356 showed that JE treatment translocates DAF-16::GFP to nucleus in transgenic worms. By analyzing the downstream of daf-16, we identify that JE may regulate sod3 downstream of daf-16. Mutant worms' lifespan and transgenic reporter gene expression assays revealed that increasing SOD-3 expression was critical for extending longevity in C. elegans with JE therapy. Collectively, these data indicate that JE may have an important role in C. elegans longevity that is dependent on DAF-16 and SOD-3.

Comparative pharmacokinetics of multi-components in normal and stomach cold syndrome rats after oral administration of Zingiberis Rhizoma - Jujubae Fructus herb pair and its single herb extracts by UHPLC-MS/MS.

The Zingiberis Rhizoma - Jujubae Fructus herb pair (ZJHP) is a classic herb pair in traditional Chinese medicine. The herb pair shows the effect of dispelling cold, harmonizing the middle and improving gastrointestinal function, and is widely used for patients with stomach cold syndrome (SCS), stomachache and anemofrigid cold. The gingerols, shogaols, flavonoids and triterpenic acids are the important bioactive ingredients of ZJHP. However, few pharmacokinetic studies have been investigated in vivo for the above compounds. To comprehend the kinetics of active components and promote their curative application, a fast and sensitive ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS/MS) method was established for simultaneous determination of 12 analytes in normal and SCS rats in this study. The results showed that the pharmacokinetic parameters (Cmax, Tmax, t1/2z, MRT0-t, AUC0-t and AUC0-∞) in SCS model were significantly different from those in normal rats. In addition, the pharmacokinetics of rats given ZJHP were also varied from single herb oral administration, especially in model condition. These results indicated that the in vivo processes of the above analytes changed under pathological conditions and the compatibility of the herb pair could significantly influence the absorption of active components, which might provide an insight and further supports for the clinical application of ZJHP.

Herbal Textual Research on Jujubae Fructus in Famous Classical Formulas / 中国实验方剂学杂志

This paper made a systematic textual research on the historical evolution and changes of the name， origin， producing area， harvesting and processing methods of Jujubae Fructus used in famous classical formulas by referring to the ancient literature， so as to provide a basis for the sampling and research of the formulas containing the medicinal materials. According to textual research， there are many names of Jujubae Fructus， most of which are named by characters or producing areas， which are called Dazao. Ziziphus jujuba has always been the mainstream variety in all dynasties， and Z. jujuba var. inemmis has also been used. Considering that the differences between the two are not obvious， we can use Z. jujuba and Z. jujuba var. inemmis as the origins of Dazao. The germplasm resources of Jujubae Fructus are rich， which are distributed all over the country. Qingzhou （now Shandong）， Jinzhou （now Shanxi） Jiangzhou （now Shanxi）， Puzhou （now Shanxi） have been recorded as authentic producing areas of Jujubae Fructus in the past dynasties， especially in Shandong. At the beginning of the 21st century， the planting of Jujubae Fructus in Xinjiang gradually developed， and now has a high market recognition， becoming an emerging production area of high-quality samples. Harvest period of Jujubae Fructus is mostly August in the past dynasties， and this is basically the same as today. The main processing method is simple cleansing and drying. Through textual research， it is suggested that Jujubae Fructus in famous classical formulas should be mainly from Shandong， Shanxi and other traditional high-quality producing areas， the processing method should follow the 2020 edition of Chinese Pharmacopoeia for simple cleansing and drying.

Detoxification mechanism of Jujubae Fructus and Crotonis Semen Pulveratum based on the toxicity of gastrointestinal system and diuretic effect in mice / 药学学报

The aim of this study was to investigate the effect of Jujubae Fructus (JF) on the gastrointestinal toxicity and diuretic effect of Crotonis Semen Pulveratum (CT). Forty-eight mice were randomly divided into the control group, low dose of CT group (0.039 g·kg-1·d-1, CTL), high dose of CT group (0.078 g·kg-1·d-1, CTH), JF group (9.75 g·kg-1·d-1), low dose of CT combined with JF group (CT 0.039 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTL), high dose of CT combined with JF group (CT 0.078 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTH). On the 9th day of oral administration, the urine output of all mice was measured. After oral administration for ten days, fresh fecal samples were collected, and the 16S rDNA sequencing method was used to study the changes of intestinal bacteria when CT used alone and combined with JF. All experimental protocols were approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine. The results showed that JF slowed down the rapid diuretic effect of CT, and significantly increased serum interleukin-2 (IL-2), interleukin-6 (IL-6), gastrin (GAS), somatostatin (SS). JF also reduced small intestine injury and improved the disorder of intestinal flora caused by CT. Low dose CT combined with JF significantly decreased the relative abundance of Sphingomonas and Oscillospira. The level of Bilophila was decreased after the combined application of high dose CT and JF. The results suggest that JF exhibited a tendency to reduce the toxicity of CT in the aspects of serum immune index, intestinal movement, intestinal damage, and intestinal microflora structure. In addition, the JF could also slow down the rapid diuretic effect of CT, behaving a tendency to reduce the clinical effect of CT.

Establishment of a method for determination of triterpenic acids in Jujubae Fructus based on quantitative analysis of multi-components by single-marker / 中草药

Objective: To develop a method for the simultaneous determination of several triterpenic acids in Jujubae Fructus and provide the technical support for the quality control of Jujubae Fructus. Methods: Betulinic acid was used as the internal reference substance, and the relative correlation factors (RCF) of oleanolic acid, ursolic acid, betulonic acid, oleanonic acid, and ursonic acid were determined by HPLC-ELSD. The contents of the five components were calculated according to the RCF, respectively. The contents of these six triterpene acids in 15 batches of Jujubae Fructus were determined by the external standard method. The rationality, feasibility, and repeatability for the method of quantitative analysis of multi-components by single-marker (QAMS) were verified by comparing with the results obtained from the external standard method. Results: The reproducibility of the RCF was acceptable. For the six triterpene acids, there was no significant difference between the quantitative results with the two different methods in the 15 batches of Jujubae Fructus. Conclusion: The method established in this research is accurate and feasible that it just needs to assay single-marker (betulinic acid) for the determination of six triterpenic acids in Jujubae Fructus simultaneously. Therefore, this method is helpful for the quality control of Jujubae Fructus and could provide a new reference for the quality assess of multi components in Chinese materia medica.