Effects of Danggui-Shaoyao-San on central neuroendocrine and pharmacokinetics in female ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine formula Danggui-Shaoyao-San (DSS) has been reported to have estrogen-like effects and therapeutic effects on the symptoms of Alzheimer's disease (AD). AIM OF THE STUDY: To explore whether the central oxytocin and neuroendocrine system is involved in the modulating effects of DSS on the cognition and neuropsychiatric hebaviors in female AD rats, and to investigate the pharmacokinetics of paeoniflorin and ferulic acid in female AD rats with DSS treatment. MATERIAL AND METHODS: DSS (1.2, 3.2, 8.6 g/kg/day) was orally administered to ovariectomized (OVX) rats, and saline was orally administered to sham operation rats as control group. The Morris water maze test, novel object recognition test, and passive avoidance test were conducted for evaluation of learning and memory abilities, while elevated plus maze test and forced swim test were performed to assess anxiety- and depressive-like behaviors. ELISA kits were used to detect the levels of estrogen (E), estrogen receptor α (ERα), oxytocin (OT), oxytocin receptor (OTR), acetylcholine (Ach), acetylcholin esterase (AchE), and choline acetyl transferase (ChAT) in the cortex. The concentrations of Ach, glutamate (Glu), γ-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT), norepinephrine (NE) and dopamine (DA) in the hippocampus were assessed by HPLC-MS. The changes of neuronal morphology in the hippocampus were observed by Nissl staining. The pharmacokinetics of paeoniflorin and ferulic acid in OVX rats with DSS treatment were studied by HPLC. RESULTS: In the Morris water maze test, novel object recognition test, and passive avoidance test, OVX rats showed cognitive impairment. In the elevated plus maze test and forced swim test, the anxiety- and depressive-like behaviors of OVX rats were significant as compared to the control group. Treatment of DSS significantly imporved the cognitive deficits, and ameliorated anxiety- and depressive-like behaviors of OVX rats. The expression of E, ERα, OT, OTR, AchE and ChAT in the cortex of model group were significantly decreased, and DSS significantly reversed these changes. The concentrations of Ach, Glu, GABA, 5-HT and NE in the hippocampus of OVX rats were significantly decreased, whereas DSS significantly increased the levels of Ach, Glu, GABA, 5-HT and NE. There was no significant difference in the concentration of DA in the hippocampus among groups. Degenerating neurons in the hippocampal CA3 region were observed in OVX rats, and the number of neurons was decreased. DSS treatment reduced the degenerating neurons, and incresed the number of neurons. The MRT (0 - ∞), AUC (0 - ∞), Cmax and t1/2z values of paeoniflorin, and the AUC 0-∞ and Cmax value of ferulic acid were higher in DSS-treated OVX rats than those in the DSS-treated control rats. CONCLUSIONS: DSS improves the learning and memory ability, and attenuates anxiety- and depressive-like behaviors of OVX rats. The mechanism may be through increasing estrogen, reducing cholinergic damage, and modulating neurotransmitters. The increase in absorption and elimination time of paeoniflorin and ferulic acid in OVX rats may enhance the efficacy of DSS.

The effectiveness and safety of Tanreqing Injection combined with ganciclovir on the treatment of respiratory syncytial virus pneumonia in children: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Based on the Theory of Traditional Chinese Medicine, this study systematically evaluated the effectiveness and safety of Chinese medicine preparation Tanreqing injection combined with ganciclovir on the treatment of respiratory syncytial virus pneumonia in children, and provided new ideas and methods for the treatment of respiratory syncytial virus pneumonia (RSVP) in children. At the same time, it also studies the effectiveness and safety of the combination of Chinese and Western medicine on the treatment of related diseases from the direction of evidence-based medicine. METHODS: The relevant literature was searched by the computer in the electronic network databases, the retrieved databases include Chinese database and English database, English database includes PubMed, Cochrane Library, Embase and Web of Science. Chinese database includes: CNKI, SinoMed, WangFang Date, VIP and other networks electronic full-text database, conducting a randomized controlled trial of Tanreqing Injection combined with ganciclovir (study group) and ganciclovir alone (control group) on the treatment of RSVP in children and the retrieval time limit is set from the establishment of each database to July 1, 2020. According to the inclusion and exclusion criteria, the literature is independently searched and screened by 2 researchers, and conducting the full-text retrieval and evaluation of the research to be included, and extracting the information and checking it after reading the full-text; In case of disagreement, a third researcher will be invited to participate, and the decision is made after discussion by the 3 researchers. They were using the bias risk assessment tool provided by the Cochrane Handbook for Systematic Reviews of Interventions 3.0.2 to evaluate the selected literature. They were using RevMan 5.3 statistical software to conduct statistical analysis. RESULTS: This study will be carried out in full accordance with the steps of systematic review as required in the Cochrane Handbook for Systematic Reviews of Interventions. All research results will be published publicly in international academic journals with peer review. CONCLUSION: After the meta-analysis of Tanreqing injection combined with ganciclovir on the treatment of RSVP in children, this paper will give a scientific and objective judgment on the effectiveness and safety of the combined use of Chinese and Western medicine on the treatment of RSVP in children, to provide evidence-based medical evidence for the clinical application, effectiveness and safety of Chinese and Western medicine combined on the treatment of RSVP in children. PROSPERO REGISTRATION NUMBER: OSF platform, registration number: j2bz5.

Structural characterization and hepatoprotective activities of polysaccharides from the leaves of Toona sinensis (A. Juss) Roem.

Two polysaccharide fractions (TSP-1 and TSP-2) with molecular weights of 833.6 kDa and 81.6 kDa were isolated from Toona sinensis leaves (Meliaceae) by hot water extraction, DEAE Cellulose-52 chromatography and Sephacryl S-400 gel permeation chromatography. Structural analysis indicated that TSP-1 and TSP-2 consisted of Manp, GlcpA, Glcp, Galp, Xylp and Araf with different molar ratios. Methylation and NMR analysis revealed that the backbone of TSP-1 might consist of 1,6-linked-Glcp, 1,3,6-linked-Manp and 1,6-linked-Galp, while TSP-2 was mainly composed of 1,3,5-linked-Araf, 1,6-linked-Glcp, 1,4-linked-Xylp and 1,6-linked-Galp. Congo red assay indicated that TSP-1 and TSP-2 had no triple-helix structure, which was consistent with the results of AFM. In vivo hepatoprotective activity showed that TSP-1 and TSP-2 could improve CCl4-induced mice liver injury by reducing the activities of AST, ALT and the level of MDA, increasing the activities of SOD, GSH-Px, and CAT and the level of GSH in liver and decreasing the expression levels of TNF-α and IL-6 in liver. These results suggest that TSP-1 and TSP-2 have promising potential to serve as hepatoprotective agents.

Pharmacokinetics, tissue distribution, bioavailability, and excretion of nuciferine, an alkaloid from lotus, in rats by LC/MS/MS.

OBJECTIVE: In order to characterize the pharmacokinetics, tissue distribution, bioavailability, and excretion of nuciferine, a reliable gradient LC/MS/MS-based method was developed and validated. METHODS: Sprague-Dawley rats were intravenously injected with a bolus of nuciferine (0.2 mg/kg) and orally given a single dose of nuciferine (10.0 mg/kg). Blood samples were withdrawn via the ocular vein at specific times. Organs, including the liver, kidney, brain, lung, heart, and spleen, were collected at specific times after oral administration of 10.0 mg/kg nuciferine. The plasma and tissue samples were assayed by LC/MS/MS. RESULTS: The results indicated that nuciferine had rapid distribution and poor absorption into systemic circulation. The value of absolute bioavailability was only 1.9 ± 0.8% after administration of 10.0 mg/kg nuciferine by oral and administration of 0.2 mg/kg nuciferine intravenously (IV) to rats. The AUC0→4 h values in tissues were in the order of kidney > lung > spleen > liver > brain > heart. The majority of excretion of nuciferine (50.7%) was excreted through kidneys with parent drug after oral administration without liver metabolism. CONCLUSION: This study may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines.

Protective role of rhapontin in experimental pulmonary fibrosis in vitro and in vivo.

BACKGROUND: Pulmonary fibrosis is a scaring process related to chronic lung injury of all causes. The treatment options for pulmonary fibrosis are very limited. Rhapontin has anti-inflammatory effect and anti-proliferative activity which is widely distributed in the medicinal plants of Rheum genus in China. However, the anti-fibrotic activities of rhapontin have not been previously investigated. METHODS: The effect of rhapontin on TGF-ß1-mediated extracellular matrix (ECM) deposition in primary lung fibroblast (PLF) cells, on TGF-ß1 secretion in LPS-stimulated human THP-1 derived macrophages in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo. Fibrotic mice were induced by intratracheal instillation of bleomycin, and then treated with rhapontin (25, 50, or 100mg/kg/day) or prednisone (6.5mg/kg/day, positive drug) for 2weeks. RESULTS: In TGF-ß1 stimulated PLFs, treatment with rhapontin resulted in a reduction of ECM with a decrease in Lox2 and p-Smad2/3. In LPS activated macrophages, treatment with rhapontin reduced TGF-ß1 production. However, in vitro the attenuated ECM deposition and inflammatory response by rhapontin were closely associated with AMPK activation, and these suppression of rhapontin were significantly abolished by the AMPK inhibitor. Treatment with rhapontin for 2weeks resulted in an amelioration of the BLM-induced pulmonary fibrosis in rats with a lower Lox2, whereas a higher AMPK expression, with reductions of the pathological score, collagen deposition, TGF-ß1, α-SMA, Lox2, and HIF-1α expressions in lung tissues at fibrotic stage at 100mg/kg. CONCLUSION: In summary, rhapontin reversed ECM, as well as Lox2 proliferation in vitro and prevented pulmonary fibrosis in vivo by modulating AMPK activation and suppressing the TGF-ß/Smad pathway.

Pharmacokinetics, bioavailability and tissue distribution of geniposide following intravenous and peroral administration to rats.

In order to characterize the pharmacokinetics, bioavailability and tissue distribution of geniposide following intravenous and peroral administration to rats, a reliable gradient HPLC-based method has been developed and validated. After p.o. administration of geniposide, the peak concentration of geniposide in plasma occurred at 1 h and plasma geniposide was eliminated nearly completely within 12 h. The AUC(0→∞) values of geniposide were 6.99 ± 1.27 h · µg/ml and 6.76 ± 1.23 h · µg/ml after i.v. administration of 10 mg/kg and p.o. administration of 100 mg/kg of geniposide, respectively. The absolute oral bioavailability (%F) of geniposide was calculated as 9.67%. After p.o. administration of geniposide, the AUC(0→4h) values in tissues were in the order of kidney > spleen > liver > heart > lung > brain. This study improved the understanding of the pharmacokinetics, bioavailability and tissue distribution of geniposide in rats and may provide a meaningful basis for clinical application of such a bioactive compound of herbal medicines.

[Study on the fingerprint of honey-fried farfarae flos by HPLC].

OBJECTIVE: To establish a HPLC-FP for the determination of honey-fried Farfarae Flos. METHODS: HPLC analysis was performed on a C18 column (4.6 mm x 250 mm, 5 microm), the mobile phase consisted of 0.1% phosphoric acid solution and acetonitrile as gradient elution with the flow rate of 1.0 mL/min. The wavelength was 240 nm. RESULTS: HPLC fingerprint of honey-fried Farfarae Flos was established and the results of methodological study met the technical requirements for fingerprint. CONCLUSION: The established method can be used for quality control of honey-fried Farfarae Flos.

[A combination of arteriovenous impulse system and low-molecular-weight heparins calcium for prophylaxis of deep venous thrombosis following total knee arthroplasty].

OBJECTIVE: To analyze the effect of arteriovenous impulse system (AVIS) combined with low-molecular-weight heparins calcium (LMWHC) for prophylaxis of deep vein thrombosis (DVT) following total knee arthroplasty (TKA). METHODS: From March 2006 to March 2008, 76 cases of osteoarthritis patients (76 knees) accepted TKA, including 25 males and 51 females with an average age of 66.6 years (range, 58-79 years). The affected knees were left side in 41 cases and right side in 35 cases. They were randomly divided into experimental group and control group before surgery. Then LMWHC and rehabilitation training were routinely given in two groups before and after surgery. However, only experimental group was treated with AVIS continually during the first four days and then two times a day for 30 minutes one time during 5-7 days. At 7 days after operation, color Doppler ultrasound was used to detect the occurrence condition of DVT. RESULTS: Five cases (13.16%) had thrombosis of calf and recovered after treated with urokinase and salvia in the experimental group. Eleven cases had thrombosis of calf and 3 cases had thrombosis of whole low extremities (36.84%), and improved after treated with urokinase and salvia in the control group. There was significant difference in DVT incidence rate between two groups (P < 0.05). No pulmonary embolism or death was found in both groups. CONCLUSION: AVIS can effectively accelerate the venous blood return velocity, a combination of AVIS and LMWHC has a better effect in the prevention of DVT following TKA.