Phenol glycosides extract of Fructus Ligustri Lucidi attenuated depressive-like behaviors by suppressing neuroinflammation in hypothalamus of mice.

Depression is partially caused by inflammation in central nervous system. This study investigated the ameliorative effects of phenol glycosides (PG) from Ligustrum lucidum Ait. (Oleaceae) on neuroinflammation and depressive-like behavior in mice hypothalamus as well as the molecular mechanism. Mice were administered with PG extract for 2 weeks prior to treatment with LPS. The mice treated with PG extract showed resistance to LPS-induced reduction in body weight and LPS-induced depressive-like behaviors shown by sucrose preference, tail suspension test, forced swimming test and open field test. LPS-induced activation of microglial cells and elevation in protein expression of inflammatory cytokines including IL-1ß, RANTES and MCP-1 in hypothalamus of mice were abrogated by pre-treatment with PG extract. This extract down-regulated expression of TLR4, MyD88, NLRP3, renin and angiotensin II and decreased proportional area of Iba-1+ microglias in hypothalamus. Pre-treatment with PG extract inhibited LPS-triggered activation of CaSR/Gα11 signaling, stimulated 1-OHase expression in hypothalamus, and enhanced circulating 1,25(OH)2 D3 level. Overall, pre-treatment with PG extract ameliorated LPS-induced depressive-like behaviors by repressing neuroinflammation in mice hypothalamus which was attributed to its suppression on activation of microglia and production of inflammatory cytokines via acting on TLR4 pathway, CaSR and RAS cascade associated with improving vitamin D metabolism.

A validated UPLC-MS/MS method for quantitative determination of a potent neuroprotective agent Sarsasapogenin-AA13 in rat plasma: Application to pharmacokinetic studies.

Sarsasapogenin-AA13(AA13), a sarsasapogenin derivative, exhibited good neuroprotective and anti-inflammatory activities in vitro and therapeutic effects on learning and memory dysfunction in amyloid-ß-injected mice. A sensitive UPLC-MS/MS method was developed and validated to quantitatively determine AA13 in rat plasma and was further applied to evaluate the pharmacokinetic behaviour of AA13 in rats that were administered AA13 intravenously and orally. This method was validated to exhibit excellent linearity in the concentration range of 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL for AA13 in rat plasma. Intra-day accuracy for AA13 was in the range of 90-114%, and inter-day accuracy was in the range of 97-103 %. The relative standard deviation of intra-day and inter-day assay was less than 15%. After a single oral administration of AA13 at the dose of 25 mg/kg, Cmax of AA13 was 1266.4 ± 316.1 ng/mL. AUC0-48 h was 6928.5 ± 1990.1 h·ng/mL, and t1/2 was 10.2 ± 0.8 h. Under intravenous administration of AA13 at a dosage of 250 µg/kg, AUC0-48 h was 785.7 ± 103.3 h⋅ng/mL, and t1/2 was 20.8 ± 7.2 h. Based on the results, oral bioavailability (F %) of AA13 in rats at 25 mg/kg was 8.82 %.

[Effect of Shengqing Capsule on Serum Cholesterol Content and Hepatic Scavenger Receptor Class B of Rats with Cholesterol Calculus].

Objective To observe the effect of Shengqing Capsule (SC) on serum contents of TC, LDL-C, and HDL-C, hepatic scavenger receptor B I (SRB I ) , and CD36 in rats with cholesterol cal- culus. Methods Totally 80 mice were divided into 4 groups according to random number table, i.e., the normal group, the model group, the Western medicine (WM) group, and the Chinese medicine (CM) group, 20 in each group. Mice in the normal group were fed with common forage, while mice in the other 3 groups were fed with lithogenic diet. Mice in the CM group and the WM group were fed with SC (at the daily dose of 0.35 g/kg) and Ursodeoxycholic Acid Tablet (UDCA, at the daily dose of 39. 55 mg/kg) re- spectively for 7 weeks. The general condition and gallstone formation rate were observed. Serum contents of TC, LDL-C, and HDL-C, and protein expressions of SBR I and CD36 were detected by oxidase meth- od and Western blot respectively. Results No gallbladder stone formed in the normal group, and gall- stone formed in 15 mice of the model group with gallstone formation rate of 75%. Compared with the nor- mal group, serum contents of TC and LDL-C and protein expressions of SRB I and CD36 increased, HDL-C content decreased in the model group (P <0. 01). The gallstone formation rate was 35% (7 mice) in the WM group and 30% (6 mice) in the CM group, lower than that of the model group (75%; P <0. 05). Contents of TC and LDL-C, and protein expressions of SRB I and CD36 decreased, HDL-C content in- creased in the WM group and the CM group (P <0.01). Compared with the WM group, TC content and protein expressions of SRB I and CD36 decreased in the CM group (P <0.01). Conclusion SC could prevent and treat gallbladder stone possibly through lowering expression levels of SRB I and CD36.

[Shengqing Capsule down-regulates estrogen and progesterone receptors in epithelial tissue of gallbladder in guinea pigs with gallstone].

OBJECTIVE: To study the role of estrogen receptor (ER) and progesterone receptor (PR) in the formation of cholesterol calculus and investigate the effects of Shengqing Capsule (SQC), a Chinese patent herbal medicine with the function of soothing liver and draining gallbladder, on ER and PR expressions. METHODS: A total of 80 female guinea pigs were divided into normal control group, untreated group, ursodeoxycholic acid group (UDCA group) and SQC group. The cholesterol gallstone was induced by feeding the guinea pigs with high-fat lithogenic diet. SQC and UDCA were separately administered to the guinea pigs in the SQC group and UDCA group. After 7-week administration, all the animals were sacrificed to calculate the incidence of calculus formation and detect the expressions the ER and PR in the epithelial tissue of gallbladder by immunohistochemical method. RESULTS: Gallstone was cholesterol calculus detected by infrared spectrum. The incidence of calculus formation in the SQC group (27.78%) was significantly lower than that in the untreated group (81.25%) (X(2)=9.721 5, P=0.001 8). On the basis of Reiner standard, the expression distribution of ER and PR increased gradually from the normal control group through the SQC group and UDCA group to the untreated group. Except for the former two groups and the latter two groups, the differences between the other groups and UDCA group were statistically significant (P<0.05). Besides, the differences of positive expression rates between groups were statistically significant (P<0.05). CONCLUSION: Increased expressions of ER and PR are closely related to the formation of cholesterol stone. And Shengqing Capsule can down-regulate the expressions of ER and PR.

[Effects of Shengqing Capsule on biochemical parameters in mice with cholesterol gallstone].

OBJECTIVE: To observe the effects of Shengqing Capsule (SQC), a compound of traditional Chinese herbal medicine, on biochemical parameters in C57BL/6J mice with cholesterol gallstone. METHODS: Thirty-eight C57BL/6J mice were randomly divided into normal control group (n=10), untreated group (n=15) and SQC group (n=13). Cholesterol gallstone was induced in mice of the latter two groups by feeding high cholesterol diet. Mice in the SQC group were intragastricly administered SQC 0.22 g/(kg.d). After 8-week treatment, animals were sacrificed and sampled to calculate the incidences of stone formation. The contents of serum cholesterols and Ca(2+), and the malonaldehyde (MDA) content and superoxide dismutase (SOD) activity in liver tissues were detected. RESULTS: The incidences of stone formation were 73.33% in untreated group, 0% in normal control group, and 23.08% in the SQC group. And the INCIDENCE in untreated group was significantly higher than those in the normal control group and the SQC group (P<0.01). Contents of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the SQC group were lower than that in the untreated group (P<0.01), and high-density lipoprotein cholesterol (HDL-C) in the SQC group was higher than that in the untreated group (P<0.01). SQC could increase the SOD activity and decrease the MDA content in liver tissues, showing significant differences as compared with those in the untreated group (P<0.05). CONCLUSION: SQC can decrease the incidence of stone formation and improve the biochemical parameters, which may be one of the mechanisms in the treatment and prevention of cholesterol gallstone disease.

[Effects of different Chinese herbal medicines on biochemical parameters in guinea-pig with pigment gallstones].

OBJECTIVE: To observe the effects of Qingdan Capsule (QDC) and Yanggan Lidan Granule (YGLDG), two kinds of compound traditional Chinese herbal medicines, on biochemical parameters in guinea-pigs with pigment gallstones. METHODS: An animal model of pigment gallstones was established in male guinea-pigs by hypodermic injection of lincomycin. The guinea-pigs were randomly divided into blank control group, untreated group, QDC group and YGLDG group. There were 8 guinea-pigs in each group. After ten-day treatment, animals were sacrificed and sampled to calculate the rate of stone formation, total bilirubin (TB), unconjugated bilirubin (UCB) and Ca2+ density in bile of the four groups. RESULTS: In comparison with the untreated group, the rates of stone formation in the QDC and YGLDG groups were significantly decreased (P<0.01). TBIL, UCB and Ca2+ content of bile in both QDC and YGLD groups was also significantly decreased (P<0.05, P<0.01). CONCLUSION: QDC and YGLD have good effects on biochemical changes of animal model of pigment gallstone in reversing the lithogenesity of bile by reducing the content of TB, UCB and Ca2+, hence resulting in clinical treatment and prevention of pigment gallstone disease.

[Inhibiting effects of recipe for dispersing stagnated liver qi to promote bile flow on cholesterol gallstone formation in guinea pigs].

OBJECTIVE: To explore the mechanism of the inhibiting effects of recipe for dispersing stagnated liver qi to promote bile flow (Danshijing Tablets) on cholesterol gallstone formation and provide experimental evidence for its clinical application. METHODS: Eighty guinea pigs were randomly divided into 4 groups, which were normal control group, untreated group, ursodeoxycholic acid (UDCA)-treated group and Danshijing Tablets-treated group. The gallstones in guinea pigs were induced by high-cholesterol diet. UDCA and Danshijing Tablets were given orally to guinea pigs in the corresponding group respectively for seven weeks. Then the physical signs of the guinea pigs, the rates of gallstone formation and the histomorphological changes of the gallbladder were examined. RESULTS: The behavior of guinea pigs in the Danshijing Tablets-treated group was obviously improved and the rate of gallstone formation was significantly decreased as compared with those in both untreated and UDCA-treated groups (P<0.05). The inflammation reaction of mucous membrane in gallbladder was evidently reduced in the Danshijing Tablets-treated group and its morphological appearance turned to be approximately normal. CONCLUSION: Recipe for dispersing stagnated liver qi to promote bile flow may decrease gallstone formation. Its mechanism may be related to reducing pathologic changes in gallbladder tissues, which will reduce the damages of cholesterol to the smooth muscle in gallbladder and enhance the contractility of gallbladder.