A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction-Related Diseases.

Bile acids are commonly known as one of the vital metabolites derived from cholesterol. The role of bile acids in glycolipid metabolism and their mechanisms in liver and cholestatic diseases have been well studied. In addition, bile acids also serve as ligands of signal molecules such as FXR, TGR5, and S1PR2 to regulate some physiological processes in vivo. Recent studies have found that bile acids signaling may also play a critical role in the central nervous system. Evidence showed that some bile acids have exhibited neuroprotective effects in experimental animal models and clinical trials of many cognitive dysfunction-related diseases. Besides, alterations in bile acid metabolisms well as the expression of different bile acid receptors have been discovered as possible biomarkers for prognosis tools in multiple cognitive dysfunction-related diseases. This review summarizes biosynthesis and regulation of bile acids, receptor classification and characteristics, receptor agonists and signaling transduction, and recent findings in cognitive dysfunction-related diseases.

Neuroprotective Effects of ZiBuPiYin Recipe on db/db Mice via PI3K-Akt Signaling Pathway by Activating Grb2.

Background: Diabetes-associated cognitive decline (DACD) is one of the nervous system dysfunctions induced by diabetes mellitus with cognitive impairment as the major symptom. In a previous preliminary proteomic study, we found that endoplasmic reticulum processing and PI3K-Akt signaling pathway might be impaired in DACD pathogenesis. In addition, growth factor receptor-bound protein 2 might be a crucial protein as a molecular target of the neuroprotective effects of ZiBuPiYin recipe (ZBPYR). Methods: In this study, 6-8 weeks aged db/db mice were treated with excipients or ZBPYR for 6 weeks. Body weight and RBG were recorded weekly. Oral glucose tolerance and insulin tolerance tests were used to assess insulin sensitivity. Morris water maze (MWM) tests were used to assess memory function. The expression of Grb2, Gab2, Akt, and GSK3ß in mouse hippocampus and cerebral cortex were analyzed by Western blotting. Results: ZBPYR not only significantly reduced RGB and improved glucose tolerance and insulin resistance, but also improved spatial cognition in DACD mice. The expression of Grb2 and Gab2 in hippocampus and cerebral cortex of db/db mice was upregulated after treated with ZBPYR, and then affected the PI3K/Akt signaling pathway, and inhibited GSK3ß overactivity. Conclusions: This study showed that ZBPYR could enhance the memory and learning ability of db/db mice. Such neuroprotective effect might be related to the activation of Grb2-PI3K/Akt signaling which might provide a novel therapeutic target for the clinical treatment of DACD.

The Beneficial Effects of a Polysaccharide from Moringa oleifera Leaf on Gut Microecology in Mice.

Moringa oleifera is a natural plant with high nutritional and pharmacological value. Leaves of M. oleifera contain a variety of active substances. In our previous research, we had obtained a polysaccharide separated from M. oleifera leaf, namely MOs-2-a (1.35 × 104 Da). In this study, this polysaccharide was administrated daily to 6 week-old ICR mice for 4 weeks. Then, the body weight, immunity, intestinal digestion, and intestinal microenvironment of Institute of Cancer Research (ICR) mice were investigated. After 4 weeks of feeding intervention with the polysaccharide, the immune and intestinal digestive ability of the ICR mice were significant as shown by the organ index, digestive enzymes, and reduction of serum tumor necrosis factor-alpha and diamine oxidase levels. The polysaccharide could regulate the microbial composition of the intestinal tract in mice by increasing the bacteria that have been reported for antiobesity effects, short chain fatty acid production, and lactic acid production. These findings indicate that the polysaccharide of M. oleifera leaf might be a promising prebiotic that exhibits health promotion effects.

[Effects of pungent essential oil from three Chinese herbs on percutaneous absorption of alkaloids from Sophorae Flavescentis Radix].

To investigate the effects of essential oil from three kinds of pungent herbs,namely Menthae Haplocalycis Herba,Atractylodis Rhizoma and Cnidii Fructus,on the transdermal absorption in vitro of alkaloids from Sophorae Flavescentis Radix. The modified vertical Franz diffusion cell was used to conduct a transdermal experiment in vitro with the isolated abdominal skin of the SD rats as the transdermal absorption barrier. The effects of such three kinds of pungent essential oil on percutaneous absorption of alkaloids from Sophorae Flavescentis Radix were investigated by determining the content of 6 alkaloids( oxymatrine,oxysophocarpine,N-methylcytisine,sophoridine,matrine,and sophocarpidine) in the transdermal acceptor with ultra-performance liquid chromatography-triple quadruple mass spectrometry( UPLC-TQ-MS) technique simultaneously. With enhancement ratio( ER) as the index,their effects on promoting penetration was as follows: 1% Atractylodis Rhizoma oil > 1% Cnidii Fructus oil > 3% Azone ≈ 3% Atractylodis Rhizoma oil > 5%Atractylodis Rhizoma oil > 3% Cnidii Fructus oil ≈ 5% Cnidii Fructus oil > 3% Menthae Haplocalycis Herba oil > 5% Menthae Haplocalycis Herba oil > 1% Menthae Haplocalycis Herba oil > Blank. The results showed that these three kinds of pungent essential oil could be used as enhancers for alkaloids of Sophorae Flavescentis Radix,providing scientific guidance for improving percutaneous absorption of alkaloids from Sophorae Flavescentis Radix.

Non-invasive treatment to grade 1 essential hypertension by percutaneous laser and electric pulse to acupoint with music: A randomized controlled trial.

OBJECTIVE: To study a non-drug therapy for hypertension disease by combining percutaneous laser and electric pulse stimulation to acupoint with music, and to test the efficiency of the combining treatment to grade 1 essential hypertension. METHODS: A total of 174 patients with grade 1 essential hypertension were randomly assigned to 3 groups with a random number table after Chinese medicine (CM) syndrome differentiation: the photoelectric and musical treatment group (Group 1, with a self-developed multi-mode audio frequency pulse photoelectric therapeutic apparatus), acupuncture group (Group 2), and oral placebo group (Group 3), 58 cases per group. The curative effect of each group was evaluated by the changes of blood pressure and CM syndrome integral before and after treatment. RESULTS: Compared with Group 3, there were significant decrease of blood pressure and CM syndrome integral in Group 1 and Group 2 (P<0.01). Compared with Group 2, Group 1 showed the highest decrease in systolic pressure (P<0.017). The total effective rate of anti-hypertension in Group 1 (91.38%, 53/58) was significantly higher than that in Group 2 (74.13%, 43/58) and Group 3 (18.97%, 11/58, P<0.05 or P<0.01); and that in Group 2 was also significantly higher than that in Group 3 (P<0.01). There were significant difference in the total effective rate of CM syndrome integral in both Group 1 (93.10%, 54/58) and Group 2 (84.48%, 49/58) as compared with Group 3 (17.24%, 10/58, P<0.01), while there was no significant difference between Group 1 and Group 2 (P>0.05). CONCLUSIONS: The multi-mode audio frequency pulse photoelectric therapeutic apparatus, combining music, laser and electric pulse stimulation, is clinically useful for grade 1 essential hypertension. This "three in one" therapy method is non-invasive, easy and simple to handle. It is expected to be popularized as a new alternative treatment.

Evaluation of the influence of salt processing on pharmacokinetics of psoralen and isopsoralen in Psoralea corylifolia L.

A sensitive, specific and rapid ultra-high-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed to investigate pharmacokinetic properties of psoralen and isopsoralen, two compounds isolated from raw/salt-processed fruit of Psoralea corylifolia L. UHPLC-MS/MS was used with positive ion electrospray. The mobile phase was composed of acetonitrile and 0.1% formic acid aqueous solution and a gradient elution program at flow rate of 0.3 mL/min was applied. Multiple reaction monitoring mode was used for the quantification of psoralen, isopsoralen ([M + H](+) m/z 187.0 → m/z 131.0) and scoparone (m/z 207.0 → m/z 151.1). Scoparone served as an internal standard. The method was fully validated for its sensitivity, selectivity, stability, matrix effect and extraction recovery. The obtained results showed that salt-processed Buguzhi significantly promoted the absorption of psoralen and isopsoralen, and increased the bioavailability of these compounds.

[Evaluation analysis of alkaloids in seed of Sophora flavescens from Shanxi province and exploration of its utilization value].

According to the research strategy of resource chemistry of Chinese medicinal materials and Chinese medicinal resources recycling utilization, this study intends to explore the potential resource-oriented utilization value of the seed of Sophora flavescens by contrasting with its kindred plant S. alopecuroides. This study established a rapid UPLC-Q-TOF-MS/MS and UPLC-TQ-MS/MS method to determine the alkaloids in the seed of S. flavescens. Results of UPLC-Q-TOF-MS/MS analysis showed that the alkaloids in the seed of S. flavescens were highly similar with S. alopecuroides.In the determination of 7 kinds of alkaloids, the total content was 11.203 and 15.506 mg•g⁻¹ in the seed of S. flavescens and S. alopecuroides, respectively. The content of oxymatrine, oxysophocarpine and sophoridine is high in the seed of S. flavescens. The results indicated that the seeds of S. flavescens. could be an important material resource to obtain alkaloids.

[Analysis on pharmacokinetics-pharmacodynamics correlation of effective ingredients of Qing'e wan].

To study the pharmacokinetics of three active ingredients in Qing'e wan, namely geniposidic acid, psoralen and isopsoralen, in rats, in order to investigate their correlation in the anti-osteoporotic effect. The rats were taken blood from their eye sockets at different time points after being orally administered with raw and salt-processed Qing'e wan. Geniposidic acid, psoralen and isopsoralen in rats plasma were determined by means of UHPLC-MS/MS to draw the concentration-time curve. The proliferation rate of osteoblasts was taken as the pharmacodynamic index, and determined by MTT method to draw effect-time curve. In comparison between the effect-time curve and the concentration-time curve, the blood concentrations of geniposidic acid and psoralen were close to the peak when the cell proliferation rate reached its peak, indicating a good correlation between them. The peak blood concentration of isopsoralen was slightly lagging behind the peak of efficacy. According to the correlation analysis after fitting the effect-time curve and the concentration-time curve, salt-processed Qing'e wan had a better correlation than the raw one. The above experimental results showed that the effect-time curve and the concentration-time curve of geniposidic acid and psoralen had a good correlation, and the correlation of salt-processed Qing'e wan was better than the raw one.

[Analysis and evaluation of alkaloids and flavonoids in flower of Sophora flavescens from Shanxi province].

This study intends to explore the potential resource-orientedutilization value of the flower of Sophora flavescents by analyzing alkaloids and flavonoids in the flower of S. flavescens from Shanxi province. This study established a rapid UPLC-TQ-MS/MS method that is used for determination of seven alkaloids and seven flavonoids in the flower of S.flavescens. The different florescences all have the seven detected alkaloids such as cytisine, oxy-matrine, oxy-sophocarpine, sophoridine, N-methylcytisine, matrine, sophocarpine.The total contents of detected alkaloids are as follows: flower buds 1.47%, primal flowers 1.34%, full bloomed flowers 1.17%, faded flowers 1.01%. The top three contents of alkaloids are N-methylcytisine , oxy-sophocarpine and oxymatrine, accounting for about 83% of the total amount of detected alkaloids. All the samples in different florescences have the seven detected flavonoids such as rutin, luteolin, quercetin, isoquercitrin, trifolirhizin, kurarinone, and kushenol I. The total contents of detected alkaloids are as follows: flower buds 495.2 µg•g⁻¹, primal flowers 313.7 µg•g⁻¹, faded flowers 224.2 µg•g⁻¹, full bloomed flowers 193.0 µg•g⁻¹. The content of luteolinis relatively higher than other detected flavonoids, accounting for about 89%-94% of the total amount of detected flavonoids. The results indicated that the flower of S.flavescens could be an important material resource to obtain the resourceful alkaloids. This result can provide scientific basis for resource-oriented utilization and industrial development of the flower of S. flavescens.

Positive skeletal effect of two ingredients of Psoralea corylifolia L. on estrogen deficiency-induced osteoporosis and the possible mechanisms of action.

Estrogen replacement therapy (ERT) is utilized as a major regime for treatment of postmenopausal osteoporosis at present. However, long-term supplement of estrogen may cause uterine hyperplasia and hypertension leading to a high risk of endometrial cancer and breast cancer. Psoralea corylifolia L. has long been used as tonic and food additives in many countries. Previous studies had found two ingredients in P. corylifolia L.: bavachin and bakuchiol exhibited osteoblastic activity. The present study was designed to investigate the protective effect of bakuchiol and bavachin on ovariectomy-induced bone loss and explore the possible mechanism. In vivo, bakuchiol and bavachin could prevented estrogen deficiency-induced bone loss in ovariectomized rats without uterotrophic activity. In vitro studies suggested that bakuchiol and bavachin induced primary human osteoblast differentiation by up-regulating the Wnt signalling pathway. This study suggests that such a bone-protective role makes them a promising and safe estrogen supplement for the ERT.