Five new compounds from Zingiberis Rhizoma Recens and their anti-apoptotic activity.

Five new compounds, named gingerol A (1a and 1b), gingerol B (2), diphenylheptane glycoside A (3) and diphenylheptane glycoside B (4), were isolated from the acetone extract of Zingiberis Rhizoma Recens. The structures of new compounds were elucidated on the basis of spectroscopic methods including UV, IR, 1D NMR, 2D NMR and HR-ESI-MS. Compounds 2-4 could significantly decrease the apoptosis rate and increase the survival rate of human normal lung epithelial cells (BEAS-2B) at the concentration of 10 µM.

[Mechanism of Cyathulae Radix in treatment of knee osteoarthritis based on metabolomics].

Metabolomics based on ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) was employed to analyze the effect of Cyathulae Radix on serum and urine in rats with knee osteoarthritis, and to decipher the mechanism of Cyathulae Radix in the treatment of knee osteoarthritis. SD rats were randomized into a normal group, a model group, a positive drug group, and a Cyathulae Radix group. The knee osteoarthritis model was established by injecting 2% pa-pain and 0.03 mol·L~(-1) cysteine, and the serum levels of tumor necrosis factor-α(TNF-α) and matrix metalloproteinase-3(MMP-3) in the model group was measured to preliminarily evaluate the therapeutic effect of Cyathulae Radix on knee osteoarthritis. UHPLC-Q-TOF-MS was employed to establish the metabolic profile of endogenous small molecule metabolites in the four groups. Potential biomarkers were screened out by multivariate analysis methods such as partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) in combination with t-test, variable importance for projection(VIP), and fold-change. The related metabolic pathways were enriched with the help of MetaboAnalyst 5.0. The results showed that Cyathulae Radix alleviated the general signs of rats with knee osteoarthritis, and reduced the levels of TNF-α and MMP-3 in the rat serum. Twenty-eight differential metabolites that might be associated with the therapeutic effect of Cyathulae Radix were screened out from serum and urine. They were mainly involved in arginine biosynthesis, nicotinate and nicotinamide metabolism, tricarboxylic acid cycle, alanine, aspartate and glutamate metabolism, riboflavin metabolism, glyoxylate and dicarboxylate metabolism, and pyrimidine metabolism. Through metabonomics analysis, this study predicted the possible mechanism of Cyathulae Radix in the treatment of knee osteoarthritis, which laid a foundation for further research.

LncPVT1 promotes cartilage degradation in diabetic OA mice by downregulating miR-146a and activating TGF-ß/SMAD4 signaling.

INTRODUCTION: To investigate the role of LncRNA PVT1 (plasmacytoma variant translocation 1) in hyperglycemia-triggered cartilage damage using the diabetic osteoarthritis (OA) mice model. MATERIALS AND METHODS: Streptozotocin (STZ) was used to induce mouse diabetes. Knee OA model was induced through transection of anterior cruciate ligament (ACLT). Severity of arthritis was assessed histologically by Safranin O-Fast Green Staining using Mankin Scores. LncRNA PVT1 and miR-146a were detected by real-time polymerase chain reaction (PCR) in cartilage tissue. Moreover, the interaction among PVT1, miR-146a, and SMAD4 was examined by luciferase reporter assays. Mice were injected intra-articularly with ad-siRNA-PVT1 and ad-siRNA scramble control. Articular concentrations of TNF-α, IL-1, IL-6 and TGF-ß1 were determined using enzyme-linked immunosorbent assay. Levels of type II Collagen (COL2A1), TGF-ß1, p-SMAD2, SMAD2, p-SMAD3, SMAD3, SMAD4 and nuclear SMAD4 were detected by western blot analysis. RESULTS: PVT1 expression was significantly increased, whereas miR-146a was markedly decreased in diabetic OA mice than in non-diabetic OA and control. Increased PVT1 expression in diabetic OA mice was significantly associated with Mankin score and reduced miR-146a as well as Collagen alpha-1(II) (COL2A1) expressions. In vivo, intra-articular injection of ad-siRNA-PVT1 efficiently increased miR-146a and COL2A1 expressions, alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed TGF-ß/SMAD4 pathway in diabetic OA mice. CONCLUSIONS: Our results demonstrate LncRNA PVT1 is involved in cartilage degradation in diabetic OA and correlated with disease severity. Efficiency of ad-siRNA-PVT1 in controlling joint inflammation in diabetic OA mice is associated with the suppression of the expression of miR-146a, pro-inflammatory cytokines and activation of TGF-ß/SMAD4 pathway.

Qualitative analysis on chemical constituents from different polarity extracted fractions of the pulp and peel of ginger rhizomes by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

RATIONALE: Ginger pulp is the dried rhizome scraped off the skin which originates from Zingiber officinale Rosc., a Zingiberaceae plant. Ginger peel is the dried rhizome skin of Zingiber officinale Rosc. (Zingiberaceae). The present work aims to investigate the different chemical constituents that are related to the medicinal properties of the ginger pulp and ginger peel. METHODS: A rapid ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-QTOF/MS) method was developed for qualitative analysis of the constituents in different polarity extracted fractions of the pulp and peel of ginger rhizomes. RESULTS: A total of 83 compounds were identified from the pulp and peel of ginger rhizomes, including 36 diarylheptanoids, 25 gingerols and 22 other compounds. Nine of these were new compounds. In total, 46, 27, 65 and 51 compounds were identified from the crude extract, petroleum ether, ethyl acetate, and n-butanol fractions of the ginger pulp, respectively, and 60, 30, 70 and 62 compounds were identified from the crude extract, petroleum ether, ethyl acetate, n-butanol fractions of the ginger peel, respectively. Each identified compound is marked on the corresponding chromatogram. CONCLUSIONS: The integrated method is sensitive and reliable for searching the different chemical constituents from different polarity extracted fractions of the ginger pulp and ginger peel. This work may provide a significant contribution to research into the medicinal properties of the ginger pulp and ginger peel.

[A new monoterpene ester from Zingiberis Rhizoma Recens].

Five monoterpenoid compounds(1-5) were isolated and purified from the acetone fraction of the aqueous extract of Zingiberis Rhizoma Recens by MCI, Sephadex LH-20, silica gel, semi-preparative HPLC, and TLC. Their structures were identified with multiple spectroscopical methods including 1 D-NMR, 2 D-NMR, and MS. The five compounds were identified as(2E,6Z)-8-hydroxy-2,6-dimethylocta-2,6-dien-1-yl-(E)-3-(4-hydroxy-3-methoxyphenyl) acrylate(1),(2E,6E)-8-hydroxy-3,7-dimethylocta-2,6-die-noic acid(2),(E)-1,8-dihydroxy-3,7-dimethyl-2-octenoic acid(3), linalyl-ß-D-glucopyranoside(4), and ß-D-glucopyranoside-(2E)-3,7-dimethyl-2,6-octadien-1-yl(5), respectively.Compound 1 was a new monoterpene ester, and compounds 4-5 were isolated from this plant for the first time.

Four new diarylheptanoids from Rhizoma Zingiberis.

Four new diarylheptanoids, (1S, 3R, 5R, 6R)-1, 5-epoxy-3, 6 dihydroxy-1-(4-hydroxy-3, 5-dimethoxyphenyl)-7-(4-hydroxy-3-methoxyphenyl) heptane (1), (1R, 3R, 5S)-1, 5-epoxy-3-acetoxy-1-(4, 5-dihydroxy-3-methoxyphenyl)-7-(3, 4- hydroxyphenyl) heptane (2), (3R, 5S, 6R, 7S)-3, 6-epoxy-7-hydroxyl-1-(4-hydroxyphenyl)-7-(3-methoxy-4-hydroxyphenyl) heptane (3), (E)-3-keto-1-(3-methoxy-4-hydroxyphenyl)-7-(4, 5-dihydroxy-3-methoxyphenyl)-4- heptene (4), were isolated from Rhizoma Zingiberis, and their structures were determined based on HR-ESI-MS and extensive spectroscopic techniques (UV, IR, 1D-NMR and 2D-NMR). Compounds 1-4 exhibited no cytotoxicity against HepG2 cell lines.

Peptic Ulcer Is the Most Common Cause of Non-Variceal Upper-Gastrointestinal Bleeding (NVUGIB) in China.

BACKGROUND This study aimed to discover the common cause of non-variceal upper-gastrointestinal bleeding (NVUGIB) by conducting a multi-center retrospective study from 2008 to 2012. MATERIAL AND METHODS Hospitalized patients ages ≥18 years old, from 8 hospitals in China, diagnosed with NVUGIB by endoscopy from 1 January 2008 to 31 December 2012 were enrolled. Questionnaires were developed and a data-entry graphical user interface was designed by using EpiData software. RESULTS Total of 2977 hospitalized patients from 8 medical centers were included. A total of 95.47% (2842/2977) of patients were admitted to a general ward, 3.53% (105/2977) were admitted to an emergency ward, and 1.00% (31/2977) were admitted to an intensive care unit. Peptic ulcer remained the most common cause of NVUGIB (73.26%), but there was a declining trend in its constituent ratio, from 2008 to 2012. A total of 14.41% (429/2977) of patients had co-morbid conditions, 92.85% (2764/2977) used proton-pump inhibitors (PPIs) prior to endoscopic treatment, 19.65% (585/2977) underwent emergency endoscopy, and 23.45% (698/2977) received a transfusion of red blood cell suspensions. A total of 5.34% (159/2977) underwent endoscopic therapy, with a treatment rate of 16.9% in high-risk peptic ulcer patients (96/568). A total of 7.69% (237/2977) were administered aspirin, of whom 32.50% (77/237) resumed aspirin intake after gastrointestinal bleeding was controlled. The median length of hospitalization was 8 days (IQR, 5-11) and the mortality rate was 1.71% (51/2977). CONCLUSIONS Peptic ulcer was still the most common cause of NVUGIB in China. The proportion of patients with high-risk peptic ulcer bleeding who received endoscopic therapy was 16.9%. Only 19.65% of NVUGIB patients underwent emergency endoscopy.

[Study on membrane injury mechanism of total alkaloids and berberine from Coptidis Rhizoma on Aeromonas hydrophila].

To explore the antibacterial activity and mechanism of total alkaloids and berberine from Coptidis Rhizoma on Aeromonas hydrophila, and determine the effect of total alkaloids and berberine from Coptidis Rhizoma on minimum inhibitory concentrations, permeability and fluidity of cell membrane, conformation of membrane proteins and virulence factors of A. hydrophila. The results showed that both total alkaloids and berberine from Coptidis Rhizoma had antibacterial activities on A. hydrophila, with minimum inhibitory concentrations of 62.5 and 125 mg · L(-1), respectively. Total alkaloids and berberine from Coptidis Rhizoma could increase the fluidity of membrane, change the conformation of membrane porteins and increase the permeability of bacteria membrane by 24.52% and 19.66%, respectively. Besides, total alkaloids and berberine from Coptidis Rhizoma significantly decreased the hemolysis of exotoxin and the mRNA expressions of aerA and hlyA (P < 0.05, P < 0.01), the secretion of endotoxin and the mRNA expression of LpxC (P < 0.05, P < 0.01). The results suggested that the antibacterial activity of total alkaloids and berberine from Coptidis Rhizoma on A. hydrophila may be related to the bacteria membrane injury. They inhibited the bacterial growth by increasing membrane lipid fluidity and changing conformation of membrane proteins, and reduced the secretion of virulence factors of A. hydrophila to weaken the pathogenicity.

[Effect of different parts, harvesting time and processing technologies on alkaloids content of Coptis chinensis adventitious root].

OBJECTIVE: To investigate the effect of different parts, harvesting time and processing technologies on alkaloids content of Coptis chinensis adventitious root. METHODS: The content of alkaloids were analyzed by HPLC. RESULTS: The content of total alkaloids in adventitious root harvested in different time was ranged from 2.5% to 2.9%, in which that of berberine and coptisine were the highest, reaching to 1%, and that of palmatine was only 0.1%. It suggested there was no significant difference of total alkaloids at different harvesting time. Nevertheless, the difference of the alkaloids content from different parts was much significant. The content of total alkaloid of adventitious root near to rhizome was about 4%, 2 times higher than that away from rhizome (only 2%). In addition, different processing technologies would affect alkaloids content obviously. There was hardly loss of alkaloids when the fresh adventitious root was washed with water, but it would decrease alkaloids content when the dried adventitious root was washed. CONCLUSION: Medicine value of Coptis chinensis adventitious root near to rhizome is higher than that away from rhizome. And fresh Coptis chinensis adventitious root can be washed with water.

[Effects of alkaloids from coptidis rhizoma on blood lipid metabolism and low-denstity lipoprotein receptor mRNA in golden hamsters].

To study the effects of alkaloids from Coptidis Rhizoma on low-density lipoprotein receptor (LDLR) mRNA expression and antihyperlipedemic levels. The LDLR mRNA expression were detected by real time fluorescence quantitative PCR, and the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c) in serum were measured at the first and last examination. The results show that, after the drug treatment, compared with the model group, each drug group showed a lipid-lowering effect. Especially, coptisine, palmatine, jatrorrhinze were significantly reduced TC, TG, LDL-c (P < 0.05, P < 0.01), and increased HDL-c (P < 0.01). In addition, they also increased mRNA expression of the LDLR in liver and HepG2 cells. The results showed that alkaloids from Coptidis Rhizoma can regulate lipid metabolism disorder, and coptisine have the best lipid-lowering effect.

Effect of Comprehensive Nursing on Pain Relief, Comfort and Burden of Family Care of Infantile Anal Fistula.

Objective: To explore the effect of comprehensive nursing on pain relief, comfort and burden of family care of infantile anal fistula. Methods: This was a randomized, double-blind, controlled clinical trial. A total of 106 cases of children with anal fistula from January 2021 to December 2021 were selected and divided into observation group and control group, there were 53 cases in each group. The control group were underwent with routine nursing intervention. The observation group were underwent with video health education, peer support, music relaxation training, physiotherapy and auricular point pressing on the basis of routine nursing therapy and other measures (comprehensive nursing). The wound healing time, comfort score, complication rate and family care burden of two groups were compared. Results: After intervention, the scores of pain degree in the observation group were significantly lower than those in the control group (4.02 ± 0.85 vs 5.89 ± 2.36, p < 0.05), and the scores of comfort degree in the observation group were higher than those in the control group (70.23 ± 5.98 vs 46.88 ± 5.23, p < 0.05). After intervention, the wound healing time of the observation group was shorter than that of the control group (3.98 ± 0.63 vs 5.77 ± 1.02, p < 0.05), and the crying times of the observation group were less than that of the control group (1.22 ± 0.26 vs 4.02 ± 0.48, p < 0.05). After intervention, the total scores of family members' care load in the observation group were significantly lower than those in the control group (37.26 ± 4.78 vs 55.99 ± 5.02, p < 0.05). Conclusion: Comprehensive nursing can effectively promote wound healing in infantile anal fistula, reduce pain, prompt children's comfort, reduce the number of children crying, and reduce the burden of care for children's families.

Novel Sesquiterpenoids with Renoprotective Activities from the Fruits of Alpinae oxyphylla as Potent TGF-ß1/Smads Phosphorylation Inhibitors.

The fruit of Alpinia oxyphylla Miq is an important food spice in southern China and has been used in the treatment of kidney disorders for centuries. In order to discover the natural products with potent renoprotective activities in A. oxyphylla and provide some references for its usage, systematic phytochemical studies were carried out and 24 new diverse sesquiterpenoids, including seven guaiane sesquiterpenoids (1-7), 10 eudesmane sesquiterpenoids (9-13, 18, 19, and 21-23), six cadinane sesquiterpenoids (31-35 and 38), and an eremophilane sesquiterpenoid (40), along with 24 known analogues were isolated and elucidated by analysis of spectroscopic data and quantum-chemical calculations. Biological evaluation showed that 6 sesquiterpenoids could significantly inhibit the expression of extracellular matrix components, α-SMA in TGF-ß1 induced kidney proximal tubular cells (NRK-52e) at low concentrations, and 9 sesquiterpenoids could also downregulate fibronectin and collagen I in a concentration-dependent manner, showing their potential in renal fibrosis. Further action mechanism study displayed that TGF-ß1/Smads pathway might be involved in the antifibrotic effects of active sesquiterpenoids 15 and 43. These studies suggest that A. oxyphylla may have a potential to serve as a functional food in preventing renal fibrosis-associated diseases.

Dimeric diarylheptanoids with anti-inflammatory activity from Zingiber officinale.

Two previously undescribed chain diarylheptanoid derivatives (2-3), five previously undescribed dimeric diarylheptanoids (4-8), together with one known cyclic diarylheptanoid (1) were isolated from Zingiber officinale. Their structures were elucidated by extensive spectroscopic analyses (HR-ESI-MS, IR, UV, 1D and 2D NMR) and ECD calculations. Biological evaluation of compounds 1-8 revealed that compounds 2, 3 and 4 could inhibit nitrite oxide and IL-6 production in lipopolysaccharide induced RAW264.7 cells in a dose-dependent manner.

[Study on optimal processing technology of three kinds of processed coptidis rhizoma].

OBJECTIVE: To optimize the processing technology of Coptidis Rhizoma and study the effects of different adjuvants on alkaloids during processing. METHODS: The moistening time of adjuvants (A), processing temperature (B) and processing time (C) were investigated by using the single factor test method and L9 (3(4)) orthogonal experiment design with the contents of four alkaloids as indexes. RESULTS: The sequence of importance of the factors that affect the wine processed Coptidis Rhizoma (WC) was C > B > A, turmeric processed Coptidis Rhizoma (TC) and dogwood processed Coptidis Rhizoma (DC) was B > A > C. CONCLUSION: The optimal processing technology of WC, TC and DC are drying for 4 h at 130 degrees C after moistening for 90 min, drying for 3 h at 100 degrees C after moistening for 60 min and drying for 2 h at 160 degrees C after moistening for 90 min, respectively.

Two new ß-carboline alkaloids from the roots of Anemone altaica.

Two new ß-carboline alkaloids, anemonilins A and B (1-2), and two known ß-carboline alkaloids, flazine (3) and 4-(9H-ß-carbolin-l-yl)-4-oxo-butyric acid (4), were isolated from the roots of Anemone altaica. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods (1D and 2DNMR, HRESIMS). Compounds 2 and 4 significantly attenuated the growth inhibition induced by lipopolysaccharide (LPS) in normal rat kidney tubule epithelioid (NRK52e) cells (p < 0.05 or p < 0.01). Furthermore, compound 2 significantly reduced the apoptosis (p < 0.05) and the caspase-3/9 expression of NRK52e cells induced by LPS.

Unusual acetylated flavonol glucuronides, oxyphyllvonides A-H with renoprotective activities from the fruits of Alpinae oxyphylla.

As a widely consumed spice and Traditional Chinese Medicine, Alpinae oxyphylla has been used to treat conditions such as diarrhea, ulcers, dementia, and enuresis. Fruits of A. oxyphylla were phytochemically studied and the bioactive constituents against renal fibrosis were identified. Eight previously undescribed acetylated flavonol glucuronides named oxyphyllvonides A-H (1-7 and 10), two known acetylated flavonol glucuronides (8 and 9), together with seven known flavone glycosides (11-17) were isolated from the fruits of A. oxyphylla. Among them, flavonol glucuronides were discovered in Zingiberaceae for the first time. The planar structures of 1-7 and 10 were determined using HRESIMS and extensive spectroscopic techniques (UV, IR, 1D-NMR, and 2D-NMR). The absolute configurations of the sugar moiety in these compounds were determined by using LC-MS analysis of acid-hydrolyzed derivatized monosaccharides. Biological evaluation showed that 7-10, 13, 14, 16 and 17 inhibit renal fibrosis in TGF-ß1-induced kidney proximal tubular cells. In addition, 7, 8 and 14 were superior to nootkatone in inhibiting Fibronectin expression. The finding has significant relevance to our ongoing research on the anti-renal fibrosis activity of A. oxyphylla.

Seven diterpenoids from the resin of Pinus yunnanensis Franch and their anti-inflammatory activity.

Phytochemical investigation of the 95% ethanol extract from Pinus yunnanensis Franch resin induced the isolation of six previously unreported diterpenoids pinuyunnanacids K - N, P - Q, a nor-diterpenoid with a novel skeleton pinuyunnanacid O and six known analogues. Their structures were elucidated by spectroscopic analysis and computational methods, including nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, calculated NMR chemical shifts method and electronic circular dichroic (ECD) spectra. All the compounds were analyzed for anti-inflammatory activity through western blotting and cell viability, compounds 2, 10 and 12 significantly downregulated the protein expression of iNOS at the concentration of 40 µM. At the same time, compounds 10 and 12 decreased the expression of COX-2 in LPS-treated RAW264.7 (leukemia cells in mouse macrophage) cells at the concentration of 40 µM.

Diverse undescribed compounds from the rhizome of Zingiber officinale Rosc. And their anti-inflammatory activity.

Seven undescribed compounds, including a sesquiterpenoid derivative, a γ-lactone, four gingerols, and a dihydroferulic acid lactate were isolated from the rhizome of Zingiber officinale, and named gingerterpenoid G, gingerlactone A, zingibergingerols A-D and L-dihydroferulic acid lactate, respectively. Zingibergingerols (±)-B and (±)-C were two pairs of enantiomers. The structures of all compounds were determined by 1D-NMR, 2D-NMR and mass spectrometry. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves or X-ray single-crystal diffraction. Bioassay showed that gingerterpenoid G, gingerlactone A, and zingibergingerols A and B exhibited significant anti-inflammatory activity in the model of LPS-induced RAW 264.7 cells.

Analysis on Early and Late Operation Results and Risk Factors of Elderly Acute Type-A Aortic Dissection.

OBJECTIVE: To explore the early and late operation results and risk factors of elderly acute type-A aortic dissection. METHODS: The regression analysis was conducted on the data of patients diagnosed with acute type-A aortic dissection in our hospital from January 2018 to January 2020, and a total of 98 patients aged over 70 years were included in the study. The patients were listed into the early operation group (a total of 51 patients operated within 3 days after admission) and the late operation group (a total of 47 patients operated within 10 days after admission) according to the time of operation. The operation results, postoperative complications and death were compared between the two groups, and the prognosis risk factors were analyzed through Logistic multi-factor regression. RESULTS: The operative time, aortic obstruction time and extracorporeal circulation time of the late operation group were all higher than those in the early operation group (p <0.05). The postoperative complications and mortality in the late operation group (12.77%) were higher than those in the early operation group (3.92%) (p < 0.05). The Logistic multi-factor regression showed that late operation (p=0.005, OR=4.213, 95% CI=1.567~11.201), postoperative acute renal insufficiency (p=0.028, OR=3.281, 95% CI=0.937~10.283), and postoperative pulmonary infection (p=0.033, OR=1.421, 95% CI=0.417~8.329) were risk factors affecting postoperative mortality (p <0.05). CONCLUSION: The early operation can effectively reduce the postoperative complications of elderly acute type-A aortic dissection, so early operation should be performed according to the conditions of patients and hospital.

Diterpenes from Pinus kesiya var. langbianensis (A.Chev.) Gaussen ex Bui (Pinaceae) and their protective effects in LPS-treated BEAS-2B cells.

Eight previously undescribed diterpenoids, rosins A-H, and nine known diterpenoids were isolated from the resin from Pinus kesiya var. langbianensis (A.Chev.) Gaussen ex Bui (Pinaceae) extracted with 95% ethanol. Their structures were determined by nuclear magnetic resonance spectroscopy, mass spectrometry, J-based configuration analysis (JBCA), NOESY spectra, calculated NMR chemical shifts and electronic circular dichroic (ECD) spectra. All compounds were evaluated for their protective effects in LPS-treated human normal lung epithelial cells (BEAS-2B), and the cell viability was significantly increased after treatment with compounds 5, 10, 12, or 15 at a concentration of 10 µM.