Efficacy and safety of vitamin K2 for postmenopausal women with osteoporosis at a long-term follow-up: meta-analysis and systematic review.

INTRODUCTION: Vitamin K2 supplementation has been revealed to be effective in the prevention and treatment of osteoporosis in Japan, but further proof for the effectiveness of this practice is still needed. OBJECTIVE: To investigate whether vitamin K2 supplementation plays a role in maintaining bone mineral density (BMD) and reducing the incidence of fractures for postmenopausal women with osteoporosis at a long-term follow-up. MATERIALS AND METHODS: We searched systematically throughout the databases of PubMed, Cochrane library, and EMBASE from the dates of their inception to November 16 2021 in this meta-analysis and systematic review, using keywords vitamin K2 and osteoporosis. RESULTS: Nine RCTs with 6853 participants met the inclusion criteria. Vitamin K2 was associated with a significantly increased percentage change of lumbar BMD and forearm BMD (WMD 2.17, 95% CI [1.59-2.76] and WMD 1.57, 95% CI [1.15-1.99]). There were significant differences in undercarboxylated osteocalcin (uc-OC) reduction (WMD -0.96, 95% CI [-0.70 to 0.21]) and osteocalcin (OC) increment (WMD 26.52, 95% CI [17.06-35.98]). Adverse reaction analysis showed that there seemed to be higher adverse reaction rates in the vitamin K2 group (RR = 1.33, 95% CI [1.11-1.59]), but no serious adverse events related to vitamin K2 supplementation. CONCLUSION: This meta-analysis and systematic review seemed to support the hypothesis that vitamin K2 plays an important role in the maintenance and improvement of BMD, and it decreases uc-OC and increases OC significantly at a long-term follow-up. Vitamin K2 supplementation is beneficial and safe in the treatment of osteoporosis for postmenopausal women.

Effects of Silymarin, Glycyrrhizin, and Oxymatrine on the Pharmacokinetics of Ribavirin and Its Major Metabolite in Rats.

The herb-derived compounds silymarin, glycyrrhizin, and oxymatrine are widely used to treat chronic hepatitis C virus infections in China. They are often prescribed in combination with ribavirin, which has a narrow therapeutic index. We investigated the influence of these compounds on ribavirin pharmacokinetics following concurrent administration at the human dose in rats. Pharmacokinetic parameters were determined in rats following oral (p.o.) administration of ribavirin (30 mg/kg) with or without silymarin (40 mg/kg, p.o.), glycyrrhizin (15 mg/kg, intraperitoneal [i.p.]), or oxymatrine (60 mg/kg, p.o.). Compared with the animals in ribavirin group, silymarin significantly decreased the area under the plasma concentration-time curve (AUC0-t ) and the peak plasma concentration (Cmax ) of ribavirin and ribavirin base by 31.2-44.5% and 48.9-50.0%, respectively. Glycyrrhizin significantly decreased the Cmax and AUC0-t of both ribavirin and its metabolite by 35.3-37.6% and 38.6-39.8%, respectively. However, silymarin or glycyrrhizin did not change the ribavirin metabolite/parent ratios of the AUC and Cmax . Oxymatrine did not induce significant changes in ribavirin concentration, but it significantly decreased the Cmax (26.6%) and AUC (21.8%) of the metabolite. This study indicates that the therapeutic efficacy of ribavirin may be compromised by the concurrent administration of herbal medicines/dietary supplements containing silymarin, glycyrrhizin, or oxymatrine.

Preparation of a novel molecularly imprinted polymer for the highly selective extraction of baicalin.

The selective extraction of baicalin is important to its quality control especially when the matrices are complicated. In this work, a novel molecularly imprinted polymer was prepared for the selective extraction of baicalin in herbs. The molecularly imprinted polymer was synthesized by the copolymerization of 4-vinyl pyridine and ethylene glycol dimethacrylate in the presence of baicalin by a precipitation polymerization method. After the optimization of parameters for molecularly imprinted polymer preparation, including the functional monomer, porogen, sampling solvent, and washing solvent, good selectivity was obtained, with an imprinting factor of about 4, which is much better than that achieved by the bulk-polymerization method. The performances of the prepared molecularly imprinted polymers were systematically investigated, including adsorption kinetics, isotherm experiment, and Scatchard analysis. On the basis of the good adsorptive capability of the prepared molecularly imprinted polymer, it was also applied for the pretreatment of baicalin in Scutellaria baicalensis Georgi. The result showed that most of the matrices were removed and baicalin was selectively enriched.

Tyrosinase inhibitor screening in traditional Chinese medicines by electrophoretically mediated microanalysis.

A capillary-electrophoresis-based method for the screening of tyrosinase inhibitors in traditional Chinese medicines was developed. The method integrated electrophoretically mediated microanalysis with sandwich mode injection, partial filling, and rapid polarity switching techniques, and carried out on-column enzyme reaction and the separation of substrate and product. The conditions were optimized including the background electrolyte, mixing voltage, and the incubation time. Finally, the screening of nine standard natural compounds of traditional Chinese medicines was carried out. The inhibitors can be directly identified from the reduced peak area of the product compared to that obtained without any inhibitor. Chlorogenic acid (100 µM) showed inhibitory activity with the inhibitory percentage of 19.8%, while the other compounds showed no inhibitory activity. This method has great application potential in drug discovery from traditional Chinese medicines.

Novel molecularly imprinted magnetic nanoparticles for the selective extraction of protoberberine alkaloids in herbs and rat plasma.

In this work, a novel magnetic nanomaterial functionalized with a molecularly imprinted polymer was prepared for the extraction of protoberberine alkaloids. Molecularly imprinted polymers were made on the surface of Fe3 O4 nanoparticles by using berberine as template, acetonitrile/water as porogen, acrylamide as functional monomer and ethylene glycol dimethacrylate as cross-linker. The optimized molar ratio of template/functional monomer was 1:7. The polymeric magnetic nanoparticles were characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The stability and adsorption capacity of the molecularly imprinted polymers were investigated. The molecularly imprinted polymers were used as a selective sorbent for the magnetic molecularly imprinted solid-phase extraction and determination of jatrorrhizine, palmatine, and berberine. Extraction parameters were studied including loading pH, sample volume, stirring speed, and extraction time. Finally, a magnetic molecularly imprinted solid-phase extraction coupled to high-performance liquid chromatography method was developed. Under the optimized conditions, the method showed good linear range of 0.1-150 ng/mL for berberine and 0.1-100 ng/mL for jatrorrhizine and palmatine. The limit of detection was 0.01 ng/mL for berberine and 0.02 ng/mL for jatrorrhizine and palmatine. The proposed method has been applied to determine protoberberine alkaloids in Cortex phellodendri and rat plasma samples. The recoveries ranged from 87.33-102.43%, with relative standard deviation less than 4.54% in Cortex phellodendri and from 102.22-111.15% with relative standard deviation less than 4.59% in plasma.

Graphene/polydopamine-modified polytetrafluoroethylene microtube for the sensitive determination of three active components in Fructus Psoraleae by online solid-phase microextraction with high-performance liquid chromatography.

Determination of bioactive compounds in traditional Chinese medicines and biological samples is usually interfered with by coexisting components in matrices. In this work, we prepared novel multilayer functional graphene/polydopamine-modified polytetrafluoroethylene microtube for selective solid-phase microextraction of three bioactive compounds in Fructus Psoraleae. Functional graphene/polydopamine-modified polytetrafluoroethylene microtube showed good extraction efficiency toward bavachin, isobavachalcone, and bavachinin; enrichment from 357- to 737-fold was obtained for these compounds. For qualitative analysis, an online solid-phase microextraction with high-performance liquid chromatography method was developed, which showed low limits of detection of 0.02 ng/mL by using UV detection, which is significantly more sensitive than previously reported methods. The proposed method has been used to determine bavachin, isobavachalcone, and bavachinin in Fructus Psoraleae, the contents of three compounds were quantified to be 64.0, 324.0, and 384.5 µg/g; recoveries were 93.4-101.1%. The proposed method has also been applied to determine bavachin, isobavachalcone, and bavachinin in rat plasma samples after oral administration of Fructus Psoraleae.

Antitumor effect of traditional Chinese herbal medicines against lung cancer.

Traditional Chinese herbal medicine (TCHM) is used widely alone or in combination with chemotherapy to treat lung cancer in China. Meta-analysis of clinical trials of TCHM against lung cancer suggested the potential, but not confirmed therapeutic effect. To gain detailed insight into the antilung cancer effects of TCHM, we searched for preclinical studies of TCHM against lung cancer published from 1995 to 2012 and systematically analyzed published articles focusing on the antitumor effect of individual TCHM in lung cancer cell lines or animal models. Among 93 herbal components isolated from 73 Chinese herbs, we found 10 herbal compounds that showed the strongest cytotoxicity in lung cancer cell lines through apoptosis or cell cycle arrest, and agents isolated from seven Chinese herbs that inhibited the primary tumor growth more than 35% in A549 xenografted mice models. In addition, three herbal components suppressed lung cancer cell migration in vitro at the concentration without cytotoxicity. Polyphyllin I, tanshinone IIA, isochaihulactone, 25-OCH3-PPD, and andrographolide were the five TCHM compounds that showed strong antilung cancer effects both in cells and in animal models, and studies of their analogs showed their structure-activity relationships. This review summarizes and analyzes contemporary studies on the antitumor effect of individual TCHM against lung cancer and animal models, providing perspectives to better understand the TCHM effect in lung cancer treatment and develop new antilung cancer drugs from TCHM.

Identification and quantification of active alkaloids in Catharanthus roseus by liquid chromatography-ion trap mass spectrometry.

Catharanthus roseus is an important dicotyledonous medicinal plant that produces anticancer compounds. The active alkaloids vinblastine, vindoline, ajmalicine, catharanthine, and vinleurosine were identified by direct-injection ion trap-mass spectrometry (IT-MS) for collecting MS(1-2) spectra. The determinations of five alkaloids were accomplished by liquid chromatography (LC) with UV and MS detections. The analytes provided good signals corresponding to the protonated molecular ions [M+H](+) and product ions. The precursor ions and product ions for quantification of vinblastine, vindoline, ajmalicine, catharanthine, and vinleurosine were m/z 825→807, 457→397, 353→144, 337→144 and 809→748 by LC-IT-MS, respectively. Two methods were used to evaluate a number of validation characteristics (repeatability, LOD, calibration range, and recovery). MS provided a high selectivity and sensitivity for determination of five alkaloids in positive mode. After optimisation of the methods, separation, identification and quantification of the five components in C. roseus were comprehensively accomplished by HPLC with UV and MS detection.

Analysis of active alkaloids in the Menispermaceae family by nonaqueous capillary electrophoresis-ion trap mass spectrometry.

A nonaqueous CE-IT MS with a nanospray ionization interface method was developed for the identification and quantification of tetrandrine (TET), fangchinoline (FAN), and sinomenine (SIN) using berberine as internal standard. The TET, FAN, and SIN standard solutions were directly infused into IT-MS for collecting MS(1-3) spectra. The major fragment ions of analytes were confirmed and possible main cleavage pathways of fragment ions were studied. A bare fused-silica capillary was used for separation of the analytes. A sheath liquid (50% aqueous methanol containing 0.2% acetic acid) to the capillary effluent with a nanoelectrospray ionization interface was added. Separation buffer comprised 80 mM solution of ammonium acetate, in a mixture of 70% methanol, 20% ACN, and 10% water, which also contained 1% acetic acid. The CE-MS method was validated for linearity, sensitivity, accuracy, and precision, and then used to determine the content of the above components. The detection limits of TET, FAN, and SIN are 0.05, 0.08, and 0.15 µg/mL, respectively. The precision was no more than 4.67% and the mean recovery of the analytes were 95.36-99.24%. This method was successfully applied to determine TET, FAN, and SIN in real samples radix Stephaniae tetrandrae and rhizomes of Menispermum dauricum.

[History and current status of acupuncture-moxibustion in Russia and former Soviet Union].

A brief history and new developments of acupuncture moxibustion in the former Soviet Union is provided in this paper, as well as in Russia. Science of acupuncture-moxibustion was introduced into Russia after the 10th Century. After the foundation of People's Republic of China, acupuncture-moxibustion therapy has drawn widespread attention in the former Soviet Union and Russia since the 1950s. Notably, acupuncture moxibustion therapy was legalized and popularized in mid 1950s in the Soviet Union, which was gradually accepted as a part of the country's medical system. In the latest 20 years, Federal health departments have paid attention to acupuncture-moxibustion therapy and issued laws and regulations on acupuncture reflexotherapy. The number of books and journals about acupuncture-moxibustion has been increasing; clinical application of acupuncture-moxibustion has been spreading and is welcomed by people. Academic exchanges between China and Russia are more frequent, which promoted the development of science of acupuncture-moxibustion in Russia.

Synthesis and biological activities of a 3'-azido analogue of Doxorubicin against drug-resistant cancer cells.

Doxorubicin (DOX), an anthracycline antibiotic, is one of the most active anticancer chemotherapeutic agents. The clinical use of DOX, however, is limited by the dose-dependant P-glycoprotein (P-gp)-mediated resistance. Herein, a 3'-azido analogue of DOX (ADOX) was prepared from daunorubicin (DNR). ADOX exhibited potent antitumor activities in drug-sensitive (MCF-7 and K562) and drug-resistant cell lines (MCF-7/DNR, K562/DOX), respectively. The drug resistance index (DRI) values of ADOX were much lower than that of DOX. The cytotoxicity experiments of ADOX or DOX against K562/DOX, with or without P-gp inhibitor, indicated that ADOX circumvents resistance by abolishing the P-gp recognition. This conclusion was further supported by drug influx/efflux flow cytometry experiments, as well as by molecular docking of ADOX to P-gp. In vivo animal tests, ADOX exhibited higher activity and less toxicity than DOX. The current data warranted ADOX for additional pre-clinical evaluations for new drug development.

Simultaneous determination of vinblastine and its monomeric precursors vindoline and catharanthine in Catharanthus roseus by capillary electrophoresis-mass spectrometry.

Catharanthus roseus is an important dicotyledonous medicinal plant that contains various anticancer components, such as vinblastine (VLB) and its monomeric precursors (vindoline and catharanthine). A capillary electrophoresis-mass spectrometry (CE-MS) approach for the simultaneous determination of three components was developed in this work. Baseline separation for three components was achieved by using a running buffer consisting of 20 mM ammonium acetate and 1.5% acetic acid in <20 min. Quantification of three components was assigned in positive-ion mode at a protonated molecular ion [M+H](+). The CE-MS method was validated for linearity, sensitivity, accuracy and precision, and then used to determine the content of the above components. The detection limits of VLB, catharanthine and vindoline are 0.8, 0.1 and 0.1 µg/mL, respectively. The precision was not more than 4.54% and the mean recovery of the analytes was 95.04-97.04%. The CE-MS method was successfully applied to determine VLB and its monomeric precursors in real sample C. roseus.

Identification and quantification of oleanolic acid and ursolic acid in Chinese herbs by liquid chromatography-ion trap mass spectrometry.

A rapid and sensitive method for the identification and quantification of ursolic acid (UA) and oleanolic acid (OA) in Chinese herbs is described. The method combines liquid chromatography (LC) with ion trap-mass spectrometry (IT-MS) detection. The UA and OA standard solution were directly infused into IT-MS for collecting MS(n) spectra. The major fragment ions of UA and OA were confirmed by MS(n) at m/z 455, 407, 391, 377 and 363 in negative ion mode, and m/z 457, 439, 411 and 393 in positive mode, respectively. The possible main cleavage pathway of fragment ions was studied. UA and OA provided good signals corresponding to the deprotonated molecular ion [M - H](-). The method is reliable and reproducible, and the detection limit is 5 ng/mL. The method was validated in the concentration range of 0.04-40 µg/mL; intra- and inter-day precisions ranged from 0.78 to 2.15%, and the accuracy was 96.5-108.2% for UA and OA. The mean recovery of UA and OA was 97.1-106.2% with RSD less than 1.86%. An LC-IT-MS method was successfully applied to determine the UA and OA in nine Chinese herbs.

Structure-activity relationships in a series of C2-substituted gluco-configured tetrahydroimidazopyridines as ß-glucosidase inhibitors.

Inhibition of glycoside hydrolases has widespread application in treatment of diabetes, viral infections, lysosomal storage diseases and cancers. Gluco-configured tetrahydroimidazopyridines are the most potent ß-glucosidase inhibitors reported to date. Using transition state mimic strategy, a series of C2-substituted gluco-configured tetrahydroimidazopyridines were designed and synthesized. Compounds 3 (K(i)=0.64 nM) and 5 (K(i)=0.58 nM) showed stronger inhibitory potency against ß-glucosidase. Maestro 9.1 was used to study the structure-activity relationships by docking the compounds into the ß-glucosidase active sites.

[Effects of acupuncture on the pulmonary function and heart rate variability in different state of bronchial asthma].

OBJECTIVE: To observe the underlying mechanism of acupuncture technique for ventilating the lung, invigorating the spleen and tonifying the kidney in the treatment of bronchial asthma (or asthma for short). METHODS: According to the severity of the disease during the persistent stage and paracmasis, 71 outpatients and inpatients were randomized into treatment group (n = 40) and control group (n = 31). Patients of treatment group were treated with acupuncture of Quchi (LI 11), Lieque (LU 7), Yuji (LU 10), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), etc., once daily and those of control group treated with anti-asthma drugs as Cromolyn sodium, Albuterol, fenoterol, etc. Before and after 12 days of the treatment, heart rate variability (HRV) and pulmonary function were detected respectively. RESULTS: In paracmasis and mild type asthma patients, self-comparison indicated that after the treatment, total power (TP), very low frequency (VLF), triangular index (TI) and the percentage of the adjacent R-R intervals (PNN50) of HRV, and forced expiratory volume in the first second (FEV1) (% PRED), forced expiratory flow (FEF) 0.2-1.2 (L/s), FEF(75%-85%) (L/s), peak expiratory flow (PEF) (% PRED), FEF(25%) (% PRED) in treatment group increased significantly (P < 0.05, 0.01), while no significant changes of various components of both HRV and pulmonary function were found in control group (P > 0.05). Comparison between two groups showed that after the treatment, the values of TP, VLF, TI and PNN50 of HRV, and FVC (% PRED), FEV1 (% PRED), FEV1/FVC (% PRED), FEF(0.2-1.2), FEF(25%-75%), PEF (% PRED) and FEF(25%) (% PRED) in treatment group were significantly higher than those in control group (P < 0.05). In moderate and severe type asthma patients, self-comparison showed that after the treatment, TP, LF, LFnorm, VLF, LF/HF, VLF/HF, (LF + VLF)/HF, TI and PNN50 of HRV, and FVC (% PRED), FEV1 (% PRED), FEV1/FVC (% PRED), FEF(0.2-1.2), FEF(25%-75%) (% PRED), FEF(75%-85%), PEF (% PRED), FEF25% (% PRED) , FEF(50%) (%PRED and FEF(75%) (% PRED) of the pulmonary function all increased remarkably (P < 0.05, 0.01, 0.001); while in comparison with control group, LF, LFnorm, VLF, (LF + VLF)/HF and TI of HRV, and all the parameters of the pulmonary function except FEV1/FVC were significantly higher than those in control group (P < 0.05, 0.01, 0.001). No significant changes of various components of both HRV and pulmonary function were found in control group (P > 0.05). CONCLUSION: Acupuncture is significantly superior to medication in improving the pulmonary function of asthma patients with different state of disease, which is related to its function in regulating activities of the autonomic nervous system.

[Effects of acupuncture on clinical symptoms and pulmonary function in the patient of bronchial asthma].

OBJECTIVE: To explore the clinical therapeutic effect of acupuncture on bronchial asthma. Methods One hundred and four cases of asthma at persistent period and remission stage were divided into a treatment group and a control group with stratified random method of illness degrees. The treatment group were treated with antiasthma agents plus acupuncture at Quchi (LI 11), Lieque (LU 7), Yuji (LU 10), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), once each day, 10 sessions constituting one course, and the control group with anti-asthma agents at the same dose. Changes of clinical symptoms and pulmonary function after treatment were investigated. Results Clinical symptoms significantly improved, the score for asthma symptoms decreased and the wheeze in the lung reduced, severity and grading of the disease significantly improved in the treatment group with significant differences as compared with those in the control group (all P< 0.05). And the first second forced expiratory volume (FEV1), peak of forced expiratory flow rate (PEF), FEF(25%-75%) (% PRED), FEF(75%-85%) (% PRED), FEF50% (%PRED), FEF75% (% PRED) more significantly improved in the treatment group than in the control group (P < 0.05 or P < 0.01 or P < 0.001). Six months later, the incidence rate of asthma acute attack in the treatment group was lower than that in the control group (P < 0.05), and the dose of anti-asthma agents in the 50% of patients in the treatment group was reduced by 1/3-1/4. CONCLUSION: Acupuncture can improve clinical symptoms and pulmonary function and reduce the dose of anti-asthma agents, and has a certain long-term therapeutic effect.

[Effects of acupuncture for dispersing fei, invigorating pi and reinforcing shen on heart rate variability and pulmonary function in bronchial asthma patients].

OBJECTIVE: To explore the acting mechanism of acupuncture treatment for dispersing Fei, invigorating Pi and reinforcing Shen (DFIPRS) on bronchial asthma. METHODS: Seventy-one chronic asthma patients in persistent or remission period were randomly assigned to two groups with stratified method, the treated group (40 cases) and the control group (31 cases). Anti-asthmatic medicine were given to both groups and acupuncture therapy to the treated group additionally on the acupoints for DFIPRS including Quchi (Lt11), Lieque (LU7), Yuji (Lu10), Neiguan (P6), Zusanli (ST36), Sanyinjiao (Sp6) and Taixi (K13) using uniform reinforcing-reducing manipulation. The changes of heart rate variability (HRV) frequency-domain index and the pulmonary function were observed before and after treatment, and the immediate effect before and after the first needling of acupuncture was also observed in 17 patients. RESULTS: After acupuncture treatment, the indices of pulmonary function improved significantly and the function of vegetative nervous system, showed by HRV, were also elevated in the treated group (P < 0.05 or P < 0.01) and significantly superior to that in the control group after treatment (P < 0.05 or P < 0.01 ). CONCLUSION: Acupuncture therapy could significantly improve pulmonary function of asthma patients, its mechanism may be related to the regulation of vegetative nerve function.