Structural identification and combination mechanism of iron (II)-chelating Atlantic salmon (Salmo salar L.) skin active peptides.

In order to utilize salmon skin for high value, and investigate the structural identification and combination mechanism of iron (II)-chelating peptides systemically, Atlantic salmon (Salmo salar L.) skin, a by-product of Atlantic salmon processing, was treated by two-step enzymatic hydrolysis to obtain salmon skin active peptides (SSAP). Then they reacted with iron (II) to obtain iron (II)-chelating salmon skin active peptides (SSAP-Fe) with a high iron (II) chelating ability of 98.84%. The results of Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD) spectroscopy, 8-anilino-1-naphthalenesulfonic acid ammonium salt hydrate (ANS) combined fluorescence measurement, isothermal titration calorimetry (ITC) and full wavelength ultraviolet (UV) scanning showed that the structural characteristics of SSAP changed before and after chelating iron (II). Reverse phase high performance liquid chromatography (RP-HPLC) and mass spectrometry were used to identify and quantify the peptides in SSAP-Fe. Four peptide sequences (STEGGG, GIIKYGDDFMH, PGQPGIGYDGPAGPPGPPGPPGAP and QNQRESWTTCRSQSSLPDG) were identified. The content of PGQPGIGYDGPAGPPGPPGPPGAP was the highest, at 25.17 µg/mg. The pharmacokinetic and pharmacodynamic properties of these four peptides were also investigated, and the results indicated that they have satisfactory predicted ADMET properties. Molecular docking technology was used to analyze the binding sites between iron (II) and SSAP, and it was found that PGQPGIGYDGPAGPPGPPGPPGAP had the lowest predicted binding energy with iron (II) and the most stable predicted binding energy with iron (II). This results showed that the stability of SSAP-Fe were closely related to the number of covalent bonds and the types of amino acids. This study revealed the structure and combination mechanism of SSAP-Fe, and indicated that SSAP-Fe prepared by chelation may be used as a Fe supplement that can be applied in functional foods or ingredients.

Anti-Diabetic Effects and Molecular Mechanisms of Amide Alkaloids from Piper longum Based on Network Pharmacology Integrated with Cellular Assays.

Piper longum is a well-known spice and traditional medicine. It was revealed to possess anti-diabetic activity, but few information about its active component and underlying mechanism could be available. In this study, retrofractamides A (1) and C (2) isolated from P. longum showed potent inhibitory activity against PTP1B. Therefore, the potential mechanism was predicted by network pharmacology and molecular docking. PI3K/AKT was obtained as the most remarkable pathway against type 2 diabetes mellitus (T2DM), and AKT1 and GSK3ß were yielded as the top two core targets of retrofractamides A (1) and C (2). Molecular docking of compounds with AKT1 and GSK3ß showed strong binding affinity between them. Additionally, cellular experiments with a L6 cell model was conducted to further verify the above predictions. Results indicated that retrofractamides A (1) and C (2) exerted anti-diabetic effect via activating PI3K/AKT pathway, and they promoted glucose consumption, glucose uptake, glycogen synthesis and glycolysis.

Shabyar Ameliorates High Glucose Induced Retinal Pigment Epithelium Injury Through Suppressing Aldose Reductase and AMPK/mTOR/ULK1 Autophagy Pathway.

Shabyar (SBA) is a traditional medicine formula for relieving vision loss caused by factors including diabetic retinopathy (DR) in clinics. However, the mechanism of it on retina protective effect still unclear. The present study aimed to investigate whether its protective effect was related to aldose reductase (AR) inhibition and retinal pigment epithelial cell injury mediated by autophagy or not. Human retinal pigment epithelial cells (ARPE-19) induced by high glucose was used as a model in vitro, with Epalrestat (EPL, AR inhibitor) and Difrarel (DFR, DR therapeutic drug) as positive controls. Western blotting and Polyol pathway products assay showed that SBA reduced the expression of AR protein and the content of ROS, and sorbitol, increased the level of Na+-K+-ATPase and alleviated cell edema. Western blotting and DCFH-DA probe assay showed that SBA decreased pAMPK/AMPK and pULK1/ULK1 which associated with autophagy initiation, down-regulated Beclin-1, Atg3, Atg5, Atg7, LC3 II and Bax/Bcl2 ratio, and up-regulated pmTOR/mTOR, SQSTM1/p62 and mitochondrial membrane potential (MMP), reduces intracellular autophagosomes. Real-Time PCR assay showed that SBA had no significant effect on mRNA expression of AR and mTOR. These data demonstrated that SBA treatment inhibits the autophagy of ARPE-19 through the AMPK/mTOR/ULK1 signaling pathway, and reduced early-stage apoptosis occurred by high glucose. These findings reveal the protective role and mechanism of SBA on retinal pigment epithelium, and provide experimental basis for the clinical application of SBA in the treatment of DR.

Chemical Composition of the Hazelnut Kernel (Corylus avellana L.) and Its Anti-inflammatory, Antimicrobial, and Antioxidant Activities.

The chemical composition of hazelnut kernels (Corylus avellana L.) and their COX-2 inhibitory, antimicrobial, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging activities were investigated. Six previously undescribed indoleacetic acid glycosides, hazelnutins A-F (1-6), and five known compounds (7-11) were isolated from the hazelnut kernels. The structures of compounds 1-6 were successfully identified by high-resolution-electrospray ionization-mass spectrometry and NMR data, and their absolute configurations were established by electron-capture detector spectroscopy analyses in corporation with quantum chemical calculations. Furthermore, the absolute configurations of compounds 7 and 8 were unambiguously confirmed for the first time. Compounds 8-11 were discovered in hazelnut kernels for the first time. Compounds 1-5 inhibited COX-2 expression with inhibition rates ranging from 36.10 to 64.08%. Compounds 3, 4, and 8 could inhibit the proliferation of Candida albicans. Compound 11 exhibited potent antioxidant activity against ABTS and DPPH with IC50 values of 11.22 and 13.21 µmol/L, respectively. Compounds 8 and 10 exhibited moderate antioxidant activity against ABTS.

Discussing Differences of Different Traditional Chinese Medicine Schemes of COVID-19 Based on Principle of "Treatment in Accordance with Three Categories of Etiologic Factors" / 中国实验方剂学杂志

Since the outbreak of corona virus disease-2019 (COVID-19), the timely intervention of Chinese medicine has played an important role， it can significantly improve the clinical symptoms of patients, alleviate fever, cough, shorten the course of disease and reduce the conversion rate of mild disease to severe disease， moreover, it has obvious advantages in improving survival rate, prognosis and quality of life in patients. In order to make better use of the therapeutic effect of Chinese medicine and overcome the epidemic situation as soon as possible, various provinces, municipalities and autonomous regions have introduced local Chinese medicine treatment schemes in accordance with the geography, climate and epidemic situation. In this article, we have analyzed the similarities and differences among treatment schemes from the perspective of three factors, and it is believed that the onset season is the same for this disease, and the differences between treatment schemes mainly depend on geographical and climatic factors. The results showed that in seven regions of China, the early symptoms in warm and humid regions such as Central China, South China, East China and Southwest China were characterized by "wet, warm, hot, and toxic", and treatment schemes mainly adopted the recipes with clearing heat and detoxifying, strengthening spleen and removing dampness functions. The early symptoms in cold regions such as Northeast China, North China, and Northwest China were mostly characterized by "cold, wet, wind, and toxic", and the therapeutic recipes emphasized on the effects of expelling wind and cold, removing toxicity and dampness. Among them, the national plan with the Hubei epidemic situation as an important reference has gradually evolved from a single syndrome attribute of each period to both cold and hot syndromes with multiple treatment methods. With the development of the disease, epidemic toxin and toxic heat in the lungs are the main characteristics in the medium term, when the treatment mainly focuses on purging heat and removing toxins. In severe cases and advanced stage, internal block and outward desertion are the main symptoms, when the treatment mainly focuses on block dredging and relieving desertion. In the recovery period, deficiency of lung and spleen Qi, and deficiency of Qi and Yin are the main symptoms, when the treatment is mainly used to invigorate the spleen, tonify the lungs, and nourish Qi and Yin. The physical factors are mostly reflected in the prevention program, so they are rarely mentioned in the treatment program. The Chinese medicine treatment schemes of COVID-19 in different regions show obvious differences. It is of great significance to analyze these differences and sum up the corresponding laws for the differential prevention and treatment of infectious diseases like COVID-19.

Syndrome Differentiation-based Treatment of COVID-19 Based on Theory of Wenyilun / 中国实验方剂学杂志

The outbreak of corona virus disease-2019 (COVID-19) in Wuhan, China, in December 2019, is highly contagious and epidemic, and belongs to the category of "plague" in traditional Chinese medicine, which seriously threatens human life and health. In the face of this sudden public health event, based on the theory of Wenyilun, this paper analyzes the onset characteristics, transmission, and syndrome differentiation-based treatment of COVID-19 in clinical practice. According to the characteristics of this epidemic, the pathogeny of COVID-19 is "epidemic pathogenic factors", and the pathogenesis is that the epidemic suppresses the dampness. Its transmission follows the regularity of "nine transmissions between exterior and interior" recorded in Wenyilun, which can be divided into sequential transmission and reverse transmission. The course of the disease has certain regularity and stages. In the early stage, the pathogen hides in the pleurodiaphragmatic interspace, and the epidemic suppresses the dampness， the treatment shall reach the pleurodiaphragmatic interspace, clear the dampness and turbidness, diffuse the lungs and dredging the lung meridian. In the middle stage, the pathogen can be transmitted to the exterior， the treatment shall be pungent in flavor and cool in property and could relieve the exterior syndrome, so as to remove the pathogen by shivering and sweating. If the dampness toxin enters the interior and be transmitted into the heat, and caused damage to the lung meridian, obstruction of Qi in the lungs, interior excess and heat accumulation, the treatment shall dredge bowel and purge heat, and expel the pathogen out. Any delay in treatment, mistreatment or excessive pathogen can lead to pathogenic invasion into the pericardium, and cause delirium, dysphoria, reversal cold of limbs, barely palpable pulse and other critical manifestations of internal blocking causing external depletion. The treatment shall focus on both attack and supplement, open blocking and relieve depletion. In the recovery period, due to the residual pathogen and the Yin and Qi impairment caused by fever, the treatment shall prevent the recurrence of the residual pathogen, nourish Yin and blood, and restore the vital energy. During the treatment, WU You-ke put forward three principles of "removing the pathogen as the priority, and then avoiding false sweating, and caring for the spleen and stomach". The theory of Wenyilun has a systematic understanding of the pathogeny, pathogenesis, and syndrome differentiation-based treatment of "the epidemic", and provides valuable experience for fight against plagues in later generations, which is also of great significance for the prevention and treatment of COVID-19.

Mechanism of Inflammatory Storm Induced by Novel Coronavirus Pneumonia and Intervention Measures of Traditional Chinese Medicine / 中国实验方剂学杂志

Some patients with corona virus disease-2019 (COVID-19) experienced a severe exacerbation of the disease due to the occurrence of inflammatory storm during the development of the disease. They are complicated with acute respiratory distress, multiple organ dysfunction syndrome and other serious complications, with a poor prognosis and a high mortality. For the inflammation storm, western medicine mostly adopts glucocorticoids, nutritional support, artificial ventilation assistance and other measures at present. The development of artificial liver, blood purification therapy, extracorporeal membrane oxygenation and other technologies have also reduced the mortality of patients to some extent. However, due to the high requirements for equipment, the measures have not yet been widely carried out. From the perspective of traditional Chinese medicine(TCM), the basic pathogenesis of COVID-19 is epidemic toxin invasion, lung and spleen being affected by pathogens, damaging vital Qi, and pathological properties involving dampness, heat, poison, stasis and deficiency. At the stage of inflammation storm, the pathogens are abundant, while the vital Qi is deficient， and the pathogens occlude lung, and disturb the heart and mind, and blood stasis and toxicity are combined with Qi-Yin deficiency. In severe cases, even both Yin and Yang exhaustion occurs. At present, a number of studies have shown that a variety of Chinese herbal medicines have multi-target immunomodulatory effect on viral pneumonia and cytokine storm. TCM participates in whole process of the occurrence and development of inflammation storm, mainly eliminating pathogens in early stage, controlling inflammation and blocking occurrence of inflammation storm， eliminating pathogens and strengthening the body resistance to eliminate the pathological products of the inflammation storm, and promoting the dissipation and absorption of inflammation in the middle stage， and saving lives in late stage by benefiting Qi and relieving depletion, and restoring Yang and rescuing from collapse. On the basis of pathophysiological mechanism of COVID-19 inflammation storm and the theory of TCM syndrome differentiation and treatment, this paper summarized the pharmacological studies on intervention on inflammatory storm with relevant Chinese herbal medicine, Chinese medicine prescriptions and Chinese medicine preparations, and discussed the intervention measures of TCM in different development stages of inflammatory storm, in expectation of providing the guidance for clinical treatment.

Psychological Adjustment During Outbreak of COVID-19 Based on Traditional Chinese Medicine Emotion Therapy / 中国实验方剂学杂志

The outbreak of corona virus disease-2019 (COVID-19) not only endangers the public life and health, but also poses threats to the public mental health. Under the atmosphere of tension and fear, the public often produces adverse emotional reactions to psychological stress, and even has extreme behaviors, which seriously affects physical and mental health. Traditional Chinese medicine （TCM） emotional therapy is based on the TCM consciousness theory in adherence to the holistic view of "integration of mind and body". It adopts safe and effective emotional conditioning methods to regulate mood, eliminate bad emotions, maintain mental health, and enhance the body's immunity to achieve the effect of treating or preventing physical and mental diseases. It has differentiated applications in many medical fields, such as post-traumatic stress disorder, generalized anxiety disorder, cancer and hospice, with good clinical efficacy. By analyzing the theoretical origin, research status, application range of TCM sentiment therapy, as well as the current public psychological state of the COVID-19 epidemic, we innovatively proposed TCM sentiment therapies, such as calm emotion method, diversion of attention method, suggestive induction method, obedient mind method, music delight method, TCM refreshing method and auricular pressing method, and comprehensively applied them in the public psychological adjustment during the outbreak, with the aim to provide rational and effective psychological guidance, help the public to correctly understand various bad emotions during the outbreak, enhance their abilities to cope with it and adjust psychological problems, maintain a good mentality, and pass the epidemic period smoothly. At the same time, in order to make better use of the advantages of TCM sentiment therapy and benefit the public, it is advocated to widely apply TCM sentiment therapy in similar public health events and public psychological care in the daily life, for the purpose of preventing before disease outset and preventing progress of disease, and effectively protecting the physical and mental health of the people.

Chemical constituents and their pharmacological activities of plants from Cichorium genus.

Plants of genus Cichorium are famous due to their therapeutic and medicinal properties. They are used as traditional medicine and edible food. To date, several scholars concentrated on compounds belonging to coumarins, flavonoids, sesquiterpenoids, triterpenoids, steroids, organic acids and other chemical constituents. Pharmacological effects such as photo-protective, hepatoprotective, anti-diabetic and lipid lowering, antioxidant, anti-inflammation, antifungal, antimalarial, increased bone mineral density,  as well as vasorelaxant and antitumour activity were wildly reported. In this study, botanical resources, ethnopharmacological application, chemical constituents and bioactivities, as well as safety and toxicity of clinical applications of genus Cichorium were reviewed, which may provide a reliable basis for further development and utilization of Cichorium genetic resources.

Ginsenoside Rg1 attenuates chronic unpredictable mild stress-induced depressive-like effect via regulating NF-κB/NLRP3 pathway in rats.

Ginsenoside (GS Rg1), which has neuroprotection and anti-inflammation activities, is the main active ingredient of Radix Ginseng. However, its antidepressant-like effect in rats remains unclear. Our study was conducted to investigate whether GS Rg1 confers an antidepressant effect in rats exposed to a chronic unpredictable mild stress model of depression and to explore its possible mechanisms. Our results revealed that GS Rg1 treatments for 3 weeks alleviated the depression-related behaviors of chronic unpredictable mild stress-exposed rats, as indicated by increasing sucrose preference, improving locomotor activity and shortening immobile time in both the forced swimming tests and tail suspension tests. And these ameliorative effects of GS Rg1 treatment were involved with regulating chronic unpredictable mild stress-induced pro-inflammatory cytokine interleukin beta (IL-1ß) related neuro-inflammation. In addition, we further found that GS Rg1 reversed chronic unpredictable mild stress-induced IL-1ß elevation, possibly by inhibiting nuclear factor kappa B pathway activation and regulating nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome expression. In short, our results suggested that GS Rg1 exerted a potential antidepressant-like effect in chronic unpredictable mild stress rat model of depression, which may provide an insight into the potential of GS Rg1 in therapeutic implications for depression.

An Overview of the Randomized Placebo-Controlled Trials of Chinese Herbal Medicine Formula Granules.

OBJECTIVE: To summarize the characteristics and the outcomes of the Randomized Placebo-Controlled Trials of Chinese Herbal Medicine Granules manufactured by China Resources Sanjiu Pharmaceutical Co., Ltd. METHODS: Databases including China National Knowledge Infrastructure, VIP, Wanfang, PubMed, Cochrane Library, and clinicaltrials.gov were searched in March 2018 for relevant randomized controlled trials (RCTs). Two reviewers independently screened for and selected studies, extracted data, and checked data extraction. Methodological quality was evaluated using the Cochrane Risk of Bias tool. For the outcome, the characteristics of the study, the cure rate, the effectiveness rate, and advert events were described with a method of bibliometrics. Also, we performed meta-analysis only if there were ≥2 studies treated by the same intervention and evaluated by the same outcome. RESULTS: A total of 40 placebo-controlled RCTs treated for 17 diseases were included in our analysis involving 4,632 patients. 16 of 19 studies treated by CHM granules only showed positive result in patients with HBV, HCV, fever, depression, nonalcoholic fatty liver disease, AIDS, and asthma while negative result was shown in patients with migraine. 17 of 21 studies treated by combination therapy against conventional therapy showed positive result in patients with HBV, herpes simplex keratitis, COPD, liver cirrhotic ascites, Parkinson's disease, and diabetic peripheral neuropathy while negative result was shown in patients with myasthenia gravis, angina pectoris, and depression. The pooled result cannot demonstrate that the notifying kidney formula granules had the superior effect with placebo on the clearance of serum HBV DNA and HBeAg in HBV carriers with a RR (and the 95% CI) of 2.97 [0.74,11.91] and 1.99 [0.93,4.29], respectively. But, the CHM granules can reduce within-group HBV DNA levels by more than 2 lgIU/ml; the RR (and 95% CI) was 4.64 [2.89,7.45]. Qizhu granules had a significant effect on clearance of HCV RNA with a RR (and 95% CI) of 6.26 [2.16,18.16]. And, the heat-clearing and detoxifying formula granules were superior to placebo in resolution of cold symptom among patients with fever with a RR and 95% CI of 2.58 [1.40,4.74]. Based on the conventional therapy, the pooled result demonstrated that the Regulating liver formula granules were superior to placebo on the clearance of serum HBeAg in chronic hepatitis B patients with a RR (and the 95% CI) of 1.73 [1.30,2.31]. The EeChen decoction granules were superior to placebo in COPD patients with a RR (and the 95% CI) of 1.13 [1.06,1.22]. 28 of the 40 studies reported adverse events. There were 51 adverse events in CHM formula granules group or combination group (n=2,483) and 26 in control group (n=2,122) totally. Most of the adverse symptoms spontaneously resolved after completing the courses of treatment and the other adverse symptoms improved after symptomatic treatment. CONCLUSION: 16 of 19 studies treated by CHM granules only showed positive result in 7 diseases and negative result in 1 disease. 17 of 21 studies treated by combination therapy against conventional therapy showed positive result in 6 diseases and negative result in 3 diseases. However, both the absolute and relative effectiveness of CHM formula granules compared with placebo need to be considered clinically.

Low-concentration hydrogen peroxide solution for continuous bladder irrigation after transurethral resection of the prostate / 中华男科学杂志

<p><b>Objective</b>To evaluate the effectiveness and safety of low-concentration hydrogen peroxide solution (HPS) for continuous bladder irrigation after transurethral resection of the prostate (TURP).</p><p><b>METHODS</b>We retrospectively analyzed the clinical data about 148 cases of benign prostatic hyperplasia (BPH) treated by TURP from January 2013 to January 2016. Seventy-six of the patients received postoperative continuous bladder irrigation with 0.15% HPS (group A) and the other 72 with normal saline (group B). We compared the two groups of patients in their postoperative hemoglobin (Hb) levels, duration of bladder irrigation, frequency of catheter blockage, time of catheterization, and length of hospital stay.</p><p><b>RESULTS</b>There were no statistically significant differences between the two groups of patients preoperatively in the prostate volume, International Prostate Symptoms Score, maximum urinary flow rate, postvoid residual urine, or levels of serum PSA and Hb (P > 0.05). At 48 hours after operation, a significantly less reduction was observed in the Hb level in group A than in group B (［3.38 ± 2.56］ vs ［7.29 ± 6.58］ g/L, P < 0.01). The patients of group A, in comparison with those of group B, also showed remarkably shorter duration of postoperative bladder irrigation (［32.57 ± 5.99］ vs ［46.10 ± 8.79］ h, P < 0.01), lower rate of catheter blockage (3.3% vs 11.8%, P < 0.01), shorter time of catheterization (［3.74 ± 0.79］ vs ［4.79 ± 0.93］ d, P < 0.01), and fewer days of postoperative hospital stay (［4.22 ± 0.81］ vs ［4.67 ± 0.88］ d, P < 0.01).</p><p><b>CONCLUSIONS</b>Low-concentration HPS for continuous bladder irrigation after TURP can reduce blood loss, catheter blockage, bladder irrigation duration, catheterization time, and hospital stay, and therefore deserves a wide clinical application.</p>

Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway.

Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A-C (compounds A-C), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro. In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A-C. Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A-C. The results suggested that compounds A-C improved glucose metabolism through promoting synthesis of glycogen. Expression of PTP1B protein was inhibited by compounds A-C in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by compounds A-C and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the insulin-mediated induction of insulin receptor substrate-1 (IRS-1) and glycogen synthase kinase-3ß (GSK-3ß) were also suppressed by wortmannin. Western blot results indicated that compounds A-C-induced IRS-1/Akt activation was likely a consequence of PTP1B inhibition. Compounds A-C promoted glycogen synthesis through Akt-mediated GSK3 phosphorylation. Therefore, activation of PI3K/Akt insulin signaling pathway and suppression of PTP1B is the molecular mechanism that contributes to the anti-diabetic effect of compounds A-C in cellular models. The three alkaloids potentially serve as lead compounds for the development of antidiabetic drugs.

Screening and Identifying Antioxidative Components in Ginkgo biloba Pollen by DPPH-HPLC-PAD Coupled with HPLC-ESI-MS2.

The Ginkgo biloba is one of ancient trees that exists from billions of years ago, its leaf and nut are used as herbs and foods in China, while so far its pollen does not have any application except pollination. In order to evaluate the antioxidant activity of Ginkgo biloba pollen, and rapidly screen its antioxidative components, the 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability, total flavonoid, total phenol, and proanthocyanidin of Ginkgo biloba pollen were determined and compared with those of Ginkgo biloba leaf and nut, and the off-line DPPH-HPLC-PAD and HPLC-ESI-MS2 were applied for screening and identifying the antioxidant flavonoids in Ginkgo biloba pollen. The results showed that the DPPH scavenging ability of Ginkgo biloba pollen was much higher than Ginkgo biloba nut, but lower than Ginkgo biloba leaf, while the total content of flavonoid in Ginkgo biloba pollen was approximately 4.37 times higher than in Ginkgo biloba leaf. Further studies found that the major flavonol aglycone in Ginkgo biloba pollen was kaempferol, which accounted for 96.71% of the total aglycones (includes quercetin, kaempferol and isorhamnetin), and the main flavonoid components in Ginkgo biloba pollen were flavonoid glycosides. Finally, ten antioxidant peaks were screened and identified to be flavonoids (including kaempferol and nine flavonoid glycosides), so flavonoids were likely to be the main antioxidant components in GP, and among them, three novel kaempferol glycosides (peaks 1, 2, and 3) were found in Ginkgo biloba pollen for the first time, which had never been found in Ginkgo biloba.

Celecoxib prevents pressure overload-induced cardiac hypertrophy and dysfunction by inhibiting inflammation, apoptosis and oxidative stress.

To explore the effects of celecoxib on pressure overload-induced cardiac hypertrophy (CH), cardiac dysfunction and explore the possible protective mechanisms. We surgically created abdominal aortic constrictions (AAC) in rats to induce CH. Rats with CH symptoms at 4 weeks after surgery were treated with celecoxib [2 mg/100 g body-weight(BW)] daily for either 2 or 4 weeks. Survival rate, blood pressure and cardiac function were evaluated after celecoxib treatment. Animals were killed, and cardiac tissue was examined for morphological changes, cardiomyocyte apoptosis, fibrosis, inflammation and oxidative stress. Four weeks after AAC, rats had significantly higher systolic, diastolic and mean blood pressure, greater heart weight and enlarged cardiomyocytes, which were associated with cardiac dysfunction. Thus, the CH model was successfully established. Two weeks later, animals had impaired cardiac function and histopathological abnormalities including enlarged cardiomyocytes and cardiac fibrosis, which were exacerbated 2 weeks later. However, these pathological changes were remarkably prevented by the treatment of celecoxib, independent of preventing hypertension. Mechanistic studies revealed that celecoxib-induced cardiac protection against CH and cardiac dysfunction was due to inhibition of apoptosis via the murine double mimute 2/P53 pathway, inhibition of inflammation via the AKT/mTOR/NF-κB pathway and inhibition of oxidative stress via increases in nuclear factor E2-related factor-2-mediated gene expression of multiple antioxidants. Celecoxib suppresses pressure overload-induced CH by reducing apoptosis, inflammation and oxidative stress.

Diterpenoid constituents of Euphorbia macrorrhiza.

Ten diterpenoids, named macrorilone A-B, macroripremyrsinone A, macrorilathyrone A-B, macrorieuphorone A-B and macroricasbalone A-C, together with ten known diterpenoids, jatrophalone, sikkimenoids A-D, jatrophodione A, latilagascenes F, jolkinol B, 15ß-O-benzoyl-5α-hydroxyisolathyrol and jatrophalactone were isolated from the whole plant of Euphorbia macrorrhiza C.A. Mey. These diterpenoids belong to six skeleton-types, including jatropholane, premyrsinane, lathyrane, euphoractin, casbene and rhamnofolane diterpenoids. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HRESIMS spectroscopic data. The absolute configurations of macrorilone B, macroripremyrsinone A and macrorilathyrone A were established by comparing their experimental and calculated electronic circular dichroism (ECD) spectra. Several of the isolated compounds exhibited weak cytotoxicity against the KB and KBv200 cell lines with IC50 values ranging from 21.19 to 47.87µM. Some also showed multidrug resistance (MDR) reversal activity, among which macrorilathyrone B exhibited a remarkable inhibitory effect on P-gp-mediated drug exclusion.

Effect of Huanglian Jiedu Decoction on Monocyte Development in apoE Gene Knockout Mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe monocyte (Mo) development in wild type C57BL/6 mice and apoE gene knockout (apoE(-/-)) mice, and to evaluate the immuno-regulatory effect of Huanglian Jiedu Decoction (HJD) on peripheral Mo development in apoE(-/-) mice.</p><p><b>METHODS</b>Four, 8, 12, and 16 weeks old female C57BL/6 mice were set up as control groups of different ages, while 4, 8, 12, and 16 weeks old female apoE(-/-) mice were set up as hyperlipidemia groups of different ages. Four-week old female C57BL/6 mice were recruited as a blank group. Four-week old female apoE(-/-) mice were randomly divided into the control group, the Western medicine group, and the Chinese medicine group by paired comparison, 5 in each group. Equivalent clinical dose was administered to mice according to body weight. Mice in the Western medicine group were administered with Atrovastatin at the daily dose of 10 mg/kg by gastrogavage, while those in the Chinese medicine group were administered with HJD at the daily dose of 5 g/kg by gastrogavage. Body weight was detected each week. After 4 weeks blood lipids levels (such as TG, TC, LDL-C, and HDL-C), and the proportions of Mo and Ly6c(hi) were detected.</p><p><b>RESULTS</b>Compared with 4-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05). Levels of TC and TG, and the proportion of Ly6c(hi) subtype increased, but the proportion of Mo de- creased in 8-week-old apoE(-/-) mice (P <0. 05). Levels of TC, TG, and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05). Levels of TC, TG, LDL-C, and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with 8-week-old homogenic mice, the proportion of Mo decreased in 16-week-old C57BL/6 mice (P < 0.05); levels of TC and LDL-C increased in 12-week-old apoE(-/-) mice (P < 0.05); levels of TC and HDL-C increased in 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01). Compared with C57BL/6 mice of the same age, TC and TG increased, HDL-C decreased (P < 0.01) in 4-and 8-week-old apoE(-/-) mice (P < 0.01); levels of TC, TG, LDL-C increased, and HDL-C level decreased in 12- and 16-week-old apoE(-/-) mice (P < 0.05, P < 0.01); the proportion of Mo increased in 4-week-old apoE(-/-) mice (P < 0.05); proportions of Mo and Ly6c(hi) increased in 8-week-old apoE(-/-) mice (P < 0.05). Compared with the blank control group, levels of TC, TG, and LDL-C, proportions of Mo and Ly6c(hi) increased (P < 0.01, P < 0.05), but HDL-C level decreased (P <0. 01) in the control group after intervention. Compared with the control group, body weight gained less in the Western medicine group and the Chinese medicine group (P < 0.05); the proportion of Ly6c(hi) subtype decreased in the Chinese medicine group (P < 0.05).</p><p><b>CONCLUSIONS</b>In development process blood lipids levels in apoE(-/-) mice are not only associated with age. Blood lipids levels induced growth changes in natural immune system are also correlated with age. In early stage of lipids development HJD intervention could correct this special immune disorder in apoE(-/-) mice.</p>

Sini powder () decoction alleviates mood disorder of insomnia by regulating cation-chloride cotransporters in hippocampus.

OBJECTIVE: To investigate the mechanism of Sini Powder () decoction (SND) in the treatment of insomnia. METHODS: The rats were randomly divided into four groups: control, model, SND-treated, and Estazolamtreated groups (n=15 in each group). Sleep deprivation (SD) rat model was established using the modifified multiple platform method for 14 h per day for 14 days, and the behavior of the rats were observed. Na-K-Cl-cotransporter (NKCC1) and K+/Cl- cotransporter (KCC2) in the hippocampus were tested by immunohistochemistry, real-time polymerase chain reaction, and western blot. RESULTS: SD rats displayed anxiety-like behavior, which was alleviated by SND. The protein expressions of NKCC1 and KCC2 in the hippocampus were signifificantly decreased in SD rats compared with those in control rats (P<0.05); these proteins were signifificantly increased by SND (P<0.05). The mRNA expression of KCC2 was signifificantly decreased in SD rats (0.62±0.35 vs. 2.29±0.56; P=0.044), while SND showed a tendency to increase the mRNA of KCC2 in SD rats (P>0.05). By contrast, the mRNA expression of NKCC1 was signifificantly increased in the hippocampus of SD rats (6.58±1.54 vs. 2.82±0.32; P=0.011), while SND decreased the mRNA expression of NKCC1 (6.58±1.54 vs. 2.79±0.81; P=0.016). CONCLUSIONS: Chinese medicine SND could alleviate mood disorder of SD rats by regulating cation-chloride cotransporters, such as NKCC1 and KCC2. These fifindings would have major implications in the mechanism of SND to relieve insomnia.

Efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia / 中华男科学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Saw Palmetto Extract Capsules in the treatment of benign prostatic hyperplasia (BPH).</p><p><b>METHODS</b>We conducted a multi-centered open clinical study on 165 BPH patients treated with Saw Palmetto Extract Capsules at a dose of 160 mg qd for 12 weeks. At the baseline and after 6 and 12 weeks of medication, we compared the International Prostate Symptom Scores (IPSS), prostate volume, postvoid residual urine volume, urinary flow rate, quality of life scores (QOL), and adverse events between the two groups of patients.</p><p><b>RESULTS</b>Compared with the baseline, both IPSS and QOL were improved after 6 weeks of medication, and at 12 weeks, significant improvement was found in IPSS, QOL, urinary flow rate, and postvoid residual urine. Mild stomachache occurred in 1 case, which necessitated no treatment.</p><p><b>CONCLUSION</b>Saw Palmetto Extract Capsules were safe and effective for the treatment of BPH.</p>