Network pharmacology and molecular docking study on the treatment of polycystic ovary syndrome with angelica sinensis- radix rehmanniae drug pair.

This study aimed to investigate the angelica sinensis - radix rehmanniae (AR) role in polycystic ovary syndrome (PCOS), employing network pharmacology and molecular docking techniques for active ingredient, targets, and pathway prediction. AR active components were obtained through TCMSP platform and literature search. The related targets of AR and PCOS were obtained through the disease and Swiss Target Prediction databases. An "active ingredient-target" network map was constructed using Cytoscape software, and gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis was conducted through Hiplot. Finally, Auto Dock Tools software was used to conduct molecular docking between active ingredients and core targets. The main bioactive ingredients of AR in the treatment of PCOS are acteoside, baicalin, caffeic acid, cistanoside F, geniposide, etc. These ingredients involve 10 core targets, such as SRC, HSP90AA1, STAT3, MAPK1, and JUN. The effect of AR on anti-PCOS mainly involves the AGE-RAGE signaling pathway, Relaxin signaling pathway, TNF signaling pathway, and ErbB signaling pathway. Molecular docking results showed that the main active components and key targets of AR could be stably combined. AR can improve hyperandrogen status, regulate glucose homeostasis, and correct lipid metabolism and other physiological processes through multi-component, multi-target, and multi-pathway. Thus, it could play a significant role in PCOS treatment. The results of our study provide a scientific foundation for basic research and clinical applications of AR for the treatment of PCOS.

Current evidence for J147 as a potential therapeutic agent in nervous system disease: a narrative review.

Curcumin has anti-inflammatory, antioxidant, and anticancer effects and is used to treat diseases such as dermatological diseases, infection, stress, depression, and anxiety. J147, an analogue of curcumin, is designed and synthesized with better stability and bioavailability. Accumulating evidence demonstrates the potential role of J147 in the prevention and treatment of Alzheimer's disease, diabetic neuropathy, ischemic stroke, depression, anxiety, and fatty liver disease. In this narrative review, we summarized the background and biochemical properties of J147 and discussed the role and mechanism of J147 in different diseases. Overall, the mechanical attributes of J147 connote it as a potential target for the prevention and treatment of neurological diseases.

Investigation on the urinary excretion kinetics of three atractylenolides from crude and processed Atractylodis rhizoma extracts in rats by UPLC-MS/MS.

Atractylodis rhizoma is a frequently-used traditional Chinese medicine in clinical practice, which have the effect of eliminating dampness and tonifying spleen. And after being processed with wheat bran, the dryness of A. rhizoma is reduced, and the function of tonifying spleen is enhanced. Atractylenolides are the major bioactive components of A. rhizoma, including atractylenolide I (AI), atractylenolide Ⅱ (AⅡ) and atractylenolide Ⅲ (AⅢ). The present study aimed to develope a new UPLC-MS/MS method for simultaneous quantification of three atractylenolides in rat urine, and applied to the excretory kinetics in Sprague-Dawley rats after oral administration of crude and processed A. rhizoma extracts. Analytes and internal standard were detected without interference in the multiple reaction monitoring (MRM) mode with positive electrospray ionization. The excretory kinetics parameters were calculated by a urine drug analysis model of drug and statistics (DAS) 3.2.8 software. The t1/2 and Ke of three atractylenolides had no significant difference between crude and processed A. rhizoma, but the recovery accumulative excretion of them in processed A. rhizoma were apparently higher than the crude ones (p<0.05, p<0.01). The results showed that only a small amount of atractylenolides excreted in urine and processing A. rhizoma with wheat bran by stir frying could promote the urinary excretion of them.

Study on the pharmacodynamics and metabolomics of five medicinal species in Atractylodes DC. on rats with rheumatoid arthritis.

Atractylodes DC. mainly includes Atractylodis Rhizoma and Atractylodis macrocephalae Rhizoma. According to Chinese Pharmacopoeia, Atractylodis Rhizoma is the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) and Atractylodes chinensis (DC.) Koidz. (A. chinensis), while Atractylodis macrocephalae Rhizoma is the rhizome of Atractylodes macrocephala Koidz. (A. macrocephala). Although Atractylodes japonica Koidz. ex Kitam. (A. japonica) and Atractylodes coreana (Nakai) Kitam. (A. coreana) are not included in the Pharmacopoeia, they are often used as Atractylodis Rhizoma in northern China. But in Japan, A. japonica is used as Atractylodis macrocephalae Rhizoma. In order to compare the efficacy of A. japonica and A. coreana with that of Atractylodis Rhizoma and Atractylodis macrocephalae Rhizomain in Pharmacopoeia, this paper studies the anti rheumatism of the five medicinal species in Atractylodes DC., and provides the basis for the rational application of A. japonica and A. coreana. With this purpose, the rheumatoid model of rats was established by Freund's complete adjuvant. Then, Enzyme-linked immunosorbent assay (ELISA) was used to determine the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF - α), arthritis factor (RF), anti cyclic citrullinated peptide (anti-CCP), interleukin-1ß (IL-1ß), Nuclear factor-κB (NF - κB), interleukin-10 (IL-10) and Prostaglandin E2 (PGE2) in rats of each group. Ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to analyze the plasma of each group. After that, multivariate statistical analysis method was used to analyze the data. The results showed that the five medicinal species in Atractylodes DC. can reduce the levels of IL-6, IL-1 ß, PGE2 and NF - κB in the plasma of rheumatoid arthritis (RA) rats in varying degrees, among which the regulation of A. macrocephala is relatively weak. A. chinensis, A. lancea, A. coreana and A. japonica can significantly reduce the content of TNF - α, in which A. japonica and A. lancea have better and similar regulatory effects. A. chinensis and A. coreana can significantly reduce the content of RF in arthritis rats. A. coreana, A. lancea and A. japonica can significantly reduce the anti-CCP level, that is, the regulatory effect of A. coreana and A. chinensis is similar. The metabolic disorder of 11-deoxycortisol, taurocholate and other small molecules in the body of rats with RA directly affects the metabolic pathways of primary bile acid biosynthesis and steroid hormone biosynthesis, leading to the decline of immune function and other symptoms. Most of the metabolic pathways tend to be normal after oral administration of five medicinal species in Atractylodes DC. Among them, the regulating effect of A. coreana and A. chinensis is similar, while that of A. japonica and A. lancea are similar. A. macrocephala had little effect of intervention.

Fecal metabonomics study of raw and bran-fried Atractylodis Rhizoma in spleen-deficiency rats.

Processing herbal medicine is a classic characters of traditional Chinese medicine (TCM) clinic. Stir-frying with bran is a common method of processing Atractylodis Rhizoma (AR), which is considered to enhance the therapeutic effect in TCM theory. However, the processing mechanism remains unclear. In our previous study, we found that bran-fried AR was better than raw AR in regulating gut flora. To further compare the effect of raw and bran-fried AR on the symbiotic metabolism of gut flora and host, we established a fecal metabonomics method of ARs intervention on spleen-deficiency rats by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. 22 potential biomarkers of spleen-deficiency were identified under the positive and negative ion mode. Through the analysis of metabolic pathway, 6 significant changes of metabolic pathway were found, 5 of which were both improved by raw and bran-fried AR. Especially bran-fried AR was better than raw AR in the improvement of tyrosine metabolism and purine metabolism. Correlation analysis between the metabolic potential biomarkers and the microbiological biomarkers published in our previous study revealed that one of the spleen-strengthening mechanisms of ARs could be associated with the improvement of the symbiotic metabolism of gut flora and host by regulating gut-flora. The results can help us to understand the mechanism of AR intervention on spleen deficiency and the enhanced-efficacy mechanism of bran-fried AR.

Rapid Characterization and Identification of Chemical Constituents in Gentiana radix before and after Wine-Processed by UHPLC-LTQ-Orbitrap MSn.

Gentiana radix is used in traditional Chinese medicine and has functions of clearing heat and drying dampness, as well as purging liver and gallbladder fire. A highly sensitive and effective strategy for rapid screening and identification of target constituents has been developed by using ultra high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap) in crude and wine-processed Gentiana radix. Based on the accurate mass measurement (<5 ppm), retention times, and MS fragmentation ions, 52 constituents were unambiguously or tentatively characterized from Gentiana radix, including 21 iridoids, 11 flavonoids, 19 xanthones, and a triterpenoid. This study demonstrated that the established method could be a rapid, effective analytical tool for screening and characterization of compounds in the complex systems of Gentiana radix. By comparing the structure and peak areas of chemical constituents in crude and wine-processed Gentiana radix, we found that some compounds in crude and wine-processed Gentiana radix were significantly different.

Comparison of Bran-Processed and Crude Atractylodes Lancea Effects on Spleen Deficiency Syndrome in Rats.

BACKGROUND: The rhizome of Atractylodes lancea (AL) is usually used for the treatment of various diseases such as spleen deficiency syndrome (SDS). Both bran-processed and crude AL is included in Chinese Pharmacopoeia. The different efficacies of bran-processed and crude AL on SDS are largely unknown, and the mechanisms of AL effects have not been fully elucidated. OBJECTIVE: The objective of the study was to compare the effects of bran-processed and crude AL and then assess the mechanisms of treating SDS. MATERIALS AND METHODS: The model of SDS in rats was established using excessive exertion, combined with an irregular diet and intragastric administration of the extract of Sennae Folium, and different doses of bran-processed and crude AL were gavaged. The serum was analyzed by an enzyme-linked immunosorbent assay (ELISA), and small intestinal tissues were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The injury of SDS was alleviated by the treatment of bran-processed and crude AL. Compared to model group, the indexes of trypsin (TRY), amylase (AMS), vasoactive intestinal peptide (VIP), somatostatin (SS), gastrin (GAS), substance P (SP), Na+-K+-ATPase, and succinic dehydrogenase in serum of each administration group were increased by ELISA, and the mRNA expressions of VIP, SS, GAS, and SP in small intestinal tissues were increased by RT-PCR. Furthermore, in a dose-dependent manner, the bran-processed and crude AL increased the levels of TRY, AMS, VIP, and GAS and the mRNA expression levels of VIP. Compared with the crude AL, the bran-processed AL was more effective in treating SDS. CONCLUSION: Through the mechanisms of treating SDS by AL, both bran-processed and crude AL has alleviated the symptoms of SDS. SUMMARY: Both bran-processed and crude Atractylodes lancea (AL) alleviated symptoms of spleen deficiency syndrome (SDS)Comparing with crude AL, bran. processed AL was more effective in treating SDSThe efficacy of AL could be partly attributed to digestive enzyme activity, gastrointestinal hormone levels, membrane protein activity, and changes in mitochondrial activity. Abbreviations used: AL: Atractylodes lancea; TRY: Trypsin; AMS: Amylase; VIP: Vasoactive intestinal peptide; SS: Somatostatin; GAS: Gastrin; SP: Substance P; ELISA: The enzyme-linked immunosorbent assay; mRNA: Messenger ribonucleic acid; SDH: Succinic dehydrogenase; RT-PCR: Reverse transcription-polymerase chain reaction; TCM: Traditional Chinese medicine; SDS: Spleen deficiency syndrome.

Determination and Tissue Distribution Comparisons of Atractylodin after Oral Administration of Crude and Processed Atractylodes Rhizome.

BACKGROUND: Atractylodis rhizoma is one of the most often used drugs in traditional Chinese medicine. Stir frying with wheat bran is the most common processing method. To clarify the principle of processing, an experiment was carried out to compare the tissue distribution of typical constituent after oral administration of raw A. rhizoma and processed ones. OBJECTIVE: To compare the tissues distribution of atractylodin after oral administration of raw and processed A. rhizoma and clarify the processing principle of A. rhizoma. Materials and Methods: High-performance liquid chromatogram with ultraviolet detection was developed and validated for the determination of atractylodin in rat tissues. RESULTS: The atractylodin in raw and processed A. rhizoma was distributed in all tissues involved in this study. CONCLUSIONS: The concentration of atractylodin in it is the highest in the stomach and small intestine. SUMMARY: In this paper, a simple, specific, and rapid reversed phase-high-performance liquid chromatogram method with ultraviolet detection for quantification of atractylodin in rat tissue has been developed for the first time. The result indicates that the concentration of atractylodin in it is the highest in the stomach and small intestine. Abbreviations used: IS: Internal standard substance; A. rhizoma: Atractylodis rhizoma; RSD: Relative standard deviation; HPLC: High performance liquid chromatography.

Transcutaneous electrical stimulation of somatic afferent nerves in the foot relieved symptoms related to postoperative bladder spasms.

BACKGROUND: Bladder spasm is a common side effect of urological surgery. Main treatment modalities include opioids or anticholinergic medication; however, bladder spasms still occur even after these interventions. Recent studies indicate that transcutaneous stimulation of the foot can result in 50% increase in bladder capacity in healthy adults, and inhibit bladder detrusor overactivity in spinal cord injured patients. In this study, we examined the effects of transcutaneous electrical stimulation of the foot on bladder spasms related symptoms. METHODS: Sixty-six male patients who underwent prostate or bladder surgeries due to benign prostatic hyperplasia or bladder diseases were randomly divided into two groups: the control group (n = 36) and the treatment group (n = 30). The control group received the routine postoperative care. The treatment group received daily transcutaneous electrical stimulation of the foot during 3 days after surgery; each time lasted for 60 min. All patients were evaluated by the Visual Analogue Scale for pain sensation, frequency of bladder spasm episodes, and a total score of bladder spasms symptoms. RESULTS: In the control group, the patients with bladder surgery had a higher Visual Analogue Scale score than patients with prostate surgery (P = 0.024). In both treatment and control groups, the Visual Analogue Scale score, spasm frequency, and total score of bladder spasm symptoms decreased from day 1 to day 3 (P <0.001). The Visual Analogue Scale score at day 2, total score of bladder spasm symptoms at day 2 and day 3 were significantly lower in the treatment group than in the control group (P <0.05). CONCLUSION: These results provided preliminary evidence suggesting beneficial effects of stimulating somatic afferent nerves in the foot on postoperative bladder spasms. TRIAL REGISTRATION: The study was registered with Chinese Clinical Trial Registry on June 13 2016 ( http://www.chictr.org.cn/ ) (Identifier: ChiCTR-INR-16008635).

[Effects of pretreatment of electroacupuncture on bupivacaine poisoning in rats].

OBJECTIVE: To observe the effects of electroacupuncture (EA) pretreatment at different times for heart arrest induced by bupivacaine poisoning in rats. METHODS: With a randomized, blind, control study, 24 SD rats were divided into a control group, a EA for 60 min (EA 60) group and a EA for 30 min (EA 30) group, 8 cases in each one. Rats in the EA 60 group and EA 30 groups were treated with EA at bilateral "Neiguan" (PC 6), "Zusanli" (ST 36) and "Fenglong" (ST 40) for 60 min and 30 min respectively. While no treatment was given in the control group. Then rats were monitored by leadⅡelectrocardiograph; catheters were inserted into the femoral vein to open the vein access and into the carotis to monitor the arterial pressure. Three hours after EA, 10 mg/kg bupivacaine was injected through femoral vein. The mean arterial pressure (MAP) and heart rate (HR) were automatically recorded by PowerLab system. The time points when QRS widened by 20 percent and cardiac arrest and the survival rates were observed. RESULTS: After the injection of bupivacaine, five rats in the EA 60 group caught cardiac arrest,while all the rats in the other two groups caught it. The survival rates were not statistically significant among the three groups (P>0.05). The time of QRS widening by 20 percent in the EA 60 group was (87.4±14.8) s,which was longer than (63.6±14.2) s in the EA 30 group and (51.2±12.4) s in the control group (both P<0.05). From injection of bupivacaine to cardiac arrest, the time of (375.3±23.7) s in the EA 60 group and that of (328.3±47.7)s in the EA 30 group were more than (235.5±91.5) s in the control group (both P<0.05). After the injection, MAP and HR in the EA 60 group were higher than those in the EA 30 group and control group at most time points (all P<0.05). CONCLUSIONS: EA pretreatment apparently decreases the vulnerability of bupivacaine-induced heart arrest, with better protective effect of 60 min pretreatment than that of 30 min.

Vitexin reduces hypoxia-ischemia neonatal brain injury by the inhibition of HIF-1alpha in a rat pup model.

Previous studies have demonstrated that the early suppression of HIF-1α after hypoxia-ischemia (HI) injury provides neuroprotection. Vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), an HIF-1α inhibitor, is a c-glycosylated flavone that has been identified in medicinal plants. Therefore, we hypothesized that treatment with vitexin would protect against HI brain injury. Newborn rat pups were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia (8% O2 at 37 °C). Vitexin (30, 45 or 60 mg/kg) was administered intraperitoneally at 5 min or 3 h after HI. Vitexin, administered 5 min after HI, was neuroprotective as seen by decreased infarct volume evaluated at 48 h post-HI. This neuroprotection was removed when vitexin was administered 3 h after HI. Neuronal cell death, blood-brain barrier (BBB) integrity, brain edema, HIF-1α and VEGF protein levels were evaluated using a combination of Nissl staining, IgG staining, brain water content, immunohistochemistry and Western blot at 24 and 48 h after HI. The long-term effects of vitexin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests. Vitexin (45 mg/kg) ameliorated brain edema, BBB disruption and neuronal cell death; Upregulation of HIF-1α by dimethyloxalylglycine (DMOG) increased the BBB permeability and brain edema compared to HI alone. Vitexin attenuated the increase in HIF-1α and VEGF. Vitexin also had long-term effects of protecting against the loss of ipsilateral brain and improveing neurobehavioral outcomes. In conclusion, our data indicate early HIF-1α inhibition with vitexin provides both acute and long-term neuroprotection in the developing brain after neonatal HI injury.

TRPV1 promotes repetitive febrile seizures by pro-inflammatory cytokines in immature brain.

Febrile seizure (FS) is the most common seizure disorder in children, and children with FS are regarded as a high risk for the eventual development of epilepsy. Brain inflammation may be implicated in the mechanism of FS. Transient receptor potential vanilloid 1 (TRPV1) is believed to act as a monitor and regulator of body temperature. The role of inflammation in synaptic plasticity mediation indicates that TRPV1 is relevant to several nervous system diseases, such as epilepsy. Here, we report a critical role for TRPV1 in a febrile seizure mouse model and reveal increased levels of pro-inflammatory factors in the immature brain. Animals were subjected to hyperthermia for 30 min, which generates seizures lasting approximately 20 min, and then were used for experiments. To invoke frequently repetitive febrile seizures, mice are exposed to hyperthermia for three times daily at an interval of 4h between every time induced seizure, and a total of 4 days to induce. Behavioral testing for febrile seizures revealed that a TRPV1 knock-out mouse model demonstrated a prolonged onset latency and a shortened duration and seizure grade of febrile seizure when compared with wild type (WT) mice. The expression levels of both TRPV1 mRNA and protein increased after a hyperthermia-induced febrile seizure in WT mice. Notably, TRPV1 activation resulted in a significant elevation in the expression of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α and HMGB1) in the hippocampus and cortex. These data indicate that the reduction of TRPV1 expression parallels a decreased susceptibility to febrile seizures. Thus, preventative strategies might be developed for use during febrile seizures.

[Effects of Crude Atractylodis Rhizoma and Processed Atractylodis Rhizoma on AQP1 - AQP5 and Hemorheology in Healthy Rats].

OBJECTIVE: To study the different effects of crude Atractylodis Rhizoma and processed Atractylodis Rhizoma in healthy rats, in order to prove the traditional theory that the crude Atractylodis Rhizoma has dry effects and the dry effects can be weaken by processing. METHODS: Health rats had been orally administered with pure water, crude Atractylodis Rhizoma, processed Atractylodis Rhizoma and atropine. The concentration of AQP1 and AQP5 in submaxillary gland were measured by ELISA. Their index of submaxillary gland, hemorheology and moisture content of intestine were also measured. RESULTS: There were obvious differences of concentration of AQP1 and AQP5 in submaxillary gland, index of submaxillary gland, hemorheology and moisture content of intestine between the rats which had been orally administered crude Atractylodis Rhizoma and the rats administered processed Rhizoma Atractylodes. CONCLUSIONS: The dry effects of Atractylodis Rhizoma works on rats' moisture content of intestine, index of submaxillary gland and hemorheology. The dry effects can be weaken by processing.

[Narrow band imaging-assisted holmium laser resection reduced the recurrence rate of non-muscle invasive bladder cancer: a prospective, randomized controlled study].

OBJECTIVE: To compare the differential effects of narrow band imaging (NBI)-assisted holmium laser with transurethral resection on the 1-year recurrence rate of non-muscle invasive bladder cancer (NMIBC), and to evaluate the clinical values of NBI-assisted holmium laser resection for NMIBC (NBI-HoLRBt). METHODS: During the period of February 2013 to February 2014, 178 cases of NMIBC were randomly divided into NBI-HoLRBt group and white light imaging (WLI) assisted transurethral resection of bladder tumor (WLI-TURBt) group. In NBI-HoLRBt, all suspicious lesion identified by either WLI or NBI were resected with WLI and in NBI mode for lesion only visible with NBI. At the end of the procedure, a NBI cystoscopic examination was performed to assess the margins of the resection areas and to identify eventual residual lesions. In WLI-TURBt group, only WLI and TURBt were applied. All patients underwent routine follow-up with WLI and NBI cystoscopy supplemented with cytology every 3 month. The recurrence risk of patients with NMIBC subjected to either NBI-HoLRBt or WLI-TURBt was compared at 3 and 12 month. RESULTS: The 3-month and 1-year recurrence rate was 18.48% (17/92) and 38.04% (35/92) respectively in the WLI-TURBt group, it was 5.81% (5/86) and 18.60% (16/86) in the NBI-HoLRBt group (both P<0.05). In addition, the in situ recurrence rate was less in the NBI-HoLRBt than WLI-TURBt group (2.33% vs 14.13%, P<0.05). CONCLUSION: NBI-assisted holmium laser resection of bladder tumor can reduce the 3-month and 1-year recurrence risk of NMIBC and should be considered a valuable clinical therapeutic method for NMIBC.

[Studies on the chemical constituents from the seed of Forsythia suspense].

OBJECTIVE: To study the chemical constituents in the seed of Forsythia suspense. METHODS: The compounds were isolated by column chromatography on silica gel and Sephadex LH-20; Their structures were identified by spectral data and other methods. RESULTS: Seven compounds were isolated and identified as beta-Amyrin acetate (I); 20(S)-Dammar-24-ene-3beta,20-diol-3-acetate (II); 18-nor-5a, 20s-cholanic acid, 3beta-20-dihydroxy-4,4,8, 14-tetramethyl-y-lactone, acetate (III); 20S,24S-epoxydammarane-25-ol-3alpha-yl acetate (IV); betulinic acid (V); protocatechuic acid (VI); octahydro-1H,5H-dipyrrolo[1,2-a: 1',2'-d] pyrazine (VII). CONCLUSION: Compound I-VII are isolated from the seed of Forsythia suspense for the first time, and compound VII is a new natural compound.

[Study on adsorption of danshen water-soluble compounds with macroporous resin D301].

OBJECTIVE: To study the adsorption and enrichment of effective compounds of danshensu, and protocatechualdehyde from Danshen water extracts by macroporous resin D301. METHOD: The change of active compounds was observed by detecting the amount of danshensu and protocatechualdehyde with HPLC. RESULT AND CONCLUSION: Macroporous resins D301 can be used in the process of adsorbing and purifying active compounds of danshensu and protocatechualdehyde, and increase the amount of active compounds in water extracts.