Sinomenine is the main bio-active ingredient of Sinomenii Caulis and usually produced by solventextraction techniques. However, the extraction of sinomenine suffers from the lack of highly efficient and environmentall...Sinomenine is the main bio-active ingredient of Sinomenii Caulis and usually produced by solventextraction techniques. However, the extraction of sinomenine suffers from the lack of highly efficient and environmentally-benign solvents. In this work, deep eutectic solvents(DESs) based on fragrances were synthesized, hydrogen-bond donors(HBDs) and hydrogen-bond acceptors(HBAs) components of DESs were identified and their extraction ability for sinomenine was evaluated and the extraction conditions were optimized by single-factor and orthogonal design experiments. It was found that the hydrogen-bonding interaction between sinomenine and DESs was the main extraction driving force and there was no explicit relationship between the extraction ability and the hydrophobicity of the DESs. The DESs could be recycled and sinomenine could be recovered quantitatively via backextraction. High-purity sinomenine((95.0 ± 2.3)%) could be produced. These findings suggest that DESs are highly-effective solvents for the isolation of sinomenine and exhibit great potential for the extraction of other bio-active compounds.展开更多
Sinomenine hydrochloride is generally produced from Caulis Sinomenii. At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine h...Sinomenine hydrochloride is generally produced from Caulis Sinomenii. At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine hydrochloride yield. In this study, a new purification process for sinomenine hydrochloride was proposed by using the extract obtained from acid extraction of Caulis Sinomenii as the starting material.The process included the following steps: alkalization, extraction, water washing, acid–water stripping,drying, and crystallization. 1-Heptanol was used as the extractant. The distribution coefficients of sinomenine and sinomenine hydrochloride in 1-heptanol–water system were 27.4 and 0.0167, respectively.The dissociation constants of sinomenine hydrochloride were 8.27 and 11.24, respectively. Process parameters of the new purification process were optimized with experimental design. The extractant1-heptanol and sinomenine hydrochloride in the crystallization mother solution can be recycled in the new process. The purity of the obtained sinomenine hydrochloride crystals exceeded 85%, and the yield was about 70%. Compared with current industrial processes, safer extractant, less solid waste, and higher sinomenine hydrochloride yield can be achieved using the new purification process of sinomenine hydrochloride provided in this study.展开更多
AIM:To investigate the inhibitory effects of sinomenine(SIN)combined with 5-fluorouracil(5-FU)on esophageal carcinoma in vitro and in vivo.METHODS:Esophageal carcinoma(Eca-109)cells were cultured in DMEM.The single or...AIM:To investigate the inhibitory effects of sinomenine(SIN)combined with 5-fluorouracil(5-FU)on esophageal carcinoma in vitro and in vivo.METHODS:Esophageal carcinoma(Eca-109)cells were cultured in DMEM.The single or combined growth inhibition effects of SIN and 5-FU on the Eca-109 cells were examined by measuring the absorbance of CCK-8dye in living cells.Hoechst 33258 staining and an Annexin V/PI apoptosis kit were used to detect the percentage of cells undergoing apoptosis.Western blotting was used to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis.SIN at 25mg/kg and 5-FU at 12 mg/kg every 3 d,either combined or alone,was injected into nude mice and tumor growth inhibition and side effects of the drug treatment were observed.RESULTS:SIN and 5-FU,both in combination and individually,significantly inhibited the proliferation of Eca-109 cells and induced obvious apoptosis.Furthermore,the combined effects were greater than those of the individual agents(P<0.05).Annexin V/PI staining and Hoechst 33258 staining both indicated that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone were significantly different from the control(P<0.05).The up-regulation of Bax and downregulation of Bcl-2 showed that the essential mechanism of apoptosis induced by SIN and 5-FU occurs via the mitochondrial pathway.SIN and 5-FU alone significantly inhibited the growth of tumor xenografts in vivo,and the combined inhibition rate was even higher(P<0.05).During the course of chemotherapy,no obvious side effects were observed in the liver or kidneys.CONCLUSION:The combined effects of SIN and 5-FU on esophageal carcinoma were superior to those of the individual compounds,and the drug combination did not increase the side effects of chemotherapy.展开更多
Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum.It is widely used as an immunosuppressive drug for treating rheumatic and arthritic diseases.In our previous studies,we fo...Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum.It is widely used as an immunosuppressive drug for treating rheumatic and arthritic diseases.In our previous studies,we found that sinomenine reduced cellular infiltration within the spinal cord and alleviated experimental autoimmune encephalomyelitis(EAE) in rats.In this study,we further investigated the mechanisms of sinomenine treatment in EAE rats.In EAE rats,treatment with sinomenine exerted an anti-inducible NO synthase(anti-iNOS) effect,which is related to the reductions of Th1 cytokine interferon-γ(IFN-γ) and its transcription factor,T-bet,in spinal cords.Moreover,sinomenine treatment of splenocytes stimulated with anti-CD3 antibody and recombinant rat interleukin 12 reduced the expression of T-bet and IFN-γ in vitro and also reduced the capability of supernatants of splenocyte culture to induce iNOS expression by primary astrocytes.However,sinomenine had no direct inhibitory effect on iNOS produced by astrocytes cultured with IFN-γ and tumor necrosis factor α in vitro.In conclusion,the anti-iNOS effect of sinomenine on EAE is mediated via the suppression of T-bet /IFN-γ pathway.展开更多
Sinomenine(SN)has been used in the clinical treatment of systemic lupus erythematosus and rheumatoid arthritis for many years.Studies showed that SN held protective effects such as anti-inflammation,scavenging free ra...Sinomenine(SN)has been used in the clinical treatment of systemic lupus erythematosus and rheumatoid arthritis for many years.Studies showed that SN held protective effects such as anti-inflammation,scavenging free radicals and suppressing immune response in many autoimmune diseases.The purpose of the present study is to explore the mechanism of anti-inflammation of SN on lipopolysaccharide(LPS)-induced macrophages activation and investigate whether the TLR4/NF-κB signaling pathway participated in.Macrophages isolated from mouse peritoneal cavity were stimulated by 1 pg/mL LPS for 24 h.And then the cells were treated with various concentrations of SN,TLR4 inhibitor respectively for additional 48 h.Drug toxicity was detected by MTT assay and Transwell experiment was used to assess chemotaxis.Furthermore,TLR4 and MyD88 mRNA levels were detected by real-time PCR.Western blotting was used to examine TLR4,MyD88 and phosphorylated IκB protein expression in macrophages.Immunofluorescence assay was applied to observe p65 NF-κB protein expression in macrophage nucleus.We extracted macrophages with high purity and activity from the abdominal cavity of mice.SN remarkably inhibited the chemotaxis and secretion function of LPS-stimulated macrophages.It also down-regulated both the protein levels of inflammatory cytokines(TNF-α,IL-β and IL-6)and the RNA and protein levels of the key factors(TLR4,MyD88,p-IkB)in TLR4 pathway.The expression of p65 NF-κB protein in nuclei was down-regulated,which was correlated with a similar decrease in p-IκB protein level.In conclusion,SN can inhibit the LPS induced immune responses in macrophages by blocking the activated TLR4/NF-κB signaling pathway.These results may provide a therapeutic approach to regulate inflammatory responses.展开更多
The effect of Sinomenine on IL-8, IL-6, IL-2 and mIL-2R produced by peripheral blood mononuclear cells was investigated by using cell culture, radioimmunoassay and flow cytometry. It was showed that production of IL-8...The effect of Sinomenine on IL-8, IL-6, IL-2 and mIL-2R produced by peripheral blood mononuclear cells was investigated by using cell culture, radioimmunoassay and flow cytometry. It was showed that production of IL-8 and mIL-2R was inhibited, but the levels of IL-6 were enhanced by Sinomenine. Our results also demonstrated that Sinomenine did not have any effect on the production of IL-2. The study demonstrated that Sinomenine was able to regulate the production of cytokines. This may be one of the mechanisms by which Sinomenine works on rheumatoid arthritis.展开更多
Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in ...Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients.In this 24 week,randomized,placebo-controlled,double-blind clinical trial,people with mild to moderate RA were randomly assigned(1:1:1,stratified by hospital)to receive SIN(120 mg,twice daily),methotrexate(MTX)(10 mg per week),or SIN+MTX therapy.The primary outcome was the proportion of patients who achieved a 50%improvement in the American College of Rheumatology(ACR50)criteria at week 24 and who showed improvement according to the clinical disease activity index(CDAI).In this prospective subgroup analysis,we also assessed whether the 24-week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine.Of the 135 enrolled participants,38,39,and 36 patients were treated with SIN,MTX,and SIN+MTX,respectively.In the SIN-treated group,52.63%of patients achieved ACR50 after 24-weeks of treatment,which was comparable to the results in the MTX-treated and SIN+MTX-treated groups.Hepatic and gastrointestinal disorders were the main adverse events;however,the ratio of patients suffering from hepatic disorder in the SIN group(1/38)was much lower than that in the MTX(10/39)and SIN+MTX(8/36)groups.A total of 221 serum samples were collected at the four follow-up time points in the three treatments,and the levels of ornithine,citrulline,and arginine were obtained through ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS).The serum ornithine level decreased after the 24-week treatment along with a decrease in disease activity,and may reflect therapeutic responses with a sensitivity value of 80%.In conclusion,SIN revealed a comparable efficacy to MTX for treating RA patients,but with fewer side effects.In addition,the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA,which shows the value of this measure as an assessment indicator of drugs in treating RA.展开更多
BACKGROUND Rheumatoid arthritis(RA)is a prevalent clinical autoimmune disease that is commonly treated with diclofenac and methotrexate.In recent years,the application of traditional Chinese medicine in RA has receive...BACKGROUND Rheumatoid arthritis(RA)is a prevalent clinical autoimmune disease that is commonly treated with diclofenac and methotrexate.In recent years,the application of traditional Chinese medicine in RA has received widespread attention;it promotes blood circulation,strengthens the immune system,and eliminates evil.The sinomenine preparation of Zhingqeng Fengtongning is studied as a possible treatment for patients with RA.AIM To explore the value of sinomenine injection into the articular cavity for the treatment of RA.METHODS A total of 94 patients with RA treated from January 2019 to January 2021 were selected and divided into the study and control groups with 47 patients each using a simple random number table method.Both groups received conventional treatment with diclofenac sodium and methotrexate tablets.The control group received diproxone and lidocaine by intra-articular administration while the study group received an intra-articular administration of the sinomenine preparation of Zhengqing Fengning and lidocaine.χ^(2) test was used to evaluate the therapeutic effect and synovial thickness,degree of pain through the visual analog scale(VAS),blood flow grade,arthroinflammatory indexes[rheumatoid factor(RF),C-reactive protein(CRP),and erythrocyte sedimentation rate(ESR)]before and after treatment in the two groups.RESULTS The total effective rate of the study group(93.62%)was higher than that of the control group(78.72%)(P<0.05).Before treatment,there were no significant differences between the two groups in terms of synovial thickness,VAS score,blood flow grading,levels of RF,and ESR(P>0.05).After treatment,the synovial thickness and VAS score were significantly lower(P<0.05)in the study group than in the control group(2.05±0.59 mm vs 2.87±0.64 mm and 2.11±0.62 vs 2.90±0.79 scores,respectively).The rate of blood flow at grade 0 in the study group(76.60%)was higher than that in the control group(57.45%),and the rate of blood flow at grade I(10.64%)was lower than that in the control group(31.91%)(P<0.05).Furthermore,the levels of RF(55.61±6.13 U/mL),CRP(11.43±3.59 mg/L),and ESR(29.60±5.56 mm/h)in the study group were lower than those in the control group(73.04±9.23 U/mL,15.07±4.06 mg/L,36.64±6.10 mm/h,respectively)(P<0.05).CONCLUSION Sinomenine administration of Zhengqing Fengtongning in the articular cavity with conventional treatment of RA can improve ultrasonographic blood flow and synovial thickness,reduce pain,regulate inflammation,and enhance therapeutic effect.展开更多
Objective:To investigate the protective effect of sinomenine stellate ganglion block(SGB)on chronic myocardial ischemia and its related mechanism.Methods:SD male and female rats(180~200g)were randomly divided into fou...Objective:To investigate the protective effect of sinomenine stellate ganglion block(SGB)on chronic myocardial ischemia and its related mechanism.Methods:SD male and female rats(180~200g)were randomly divided into four groups:blank group,model group,lidocaine group,lidocaine+sinomenine group.The rats in blank group were fed with normal standard diet without modeling,and the other rats were fed with high-fat diet.After 8 weeks of feeding,the rats in high-fat diet group were significantly different from those in blank control group.Then they were randomly divided into 3 groups,10 rats in model group were injected with 0.9%NaCl into right stellate ganglion(RSG)After 2 weeks of continuous injection,pituitrin injection was continuously injected into sublingual vein of rats for 3 days,once every 24 hours;lidocaine group rats were injected with 0.24 mL 1%lidocaine injection in RSG,the rest was the same as model group;lidocaine+sinomenine group rats were injected with 0.24 mL 1%lidocaine injection+0.095 mL sinomenine hydrochloride+2.9 mL 0.8 mL 0.8 mL in RSG,the rest was the same as model group.At the end of the eighth week of the experiment,the rats in the high-fat diet feeding group and the standard ordinary diet feeding group were given the medicine after there was significant difference in blood lipid;before the third injection of pituitrin,the ECG changes of the rats in each group were observed;the general situation of the rats before and after the administration was observed;after the experiment,the blood of the rats in each group was taken from the abdominal aorta,and the serum oxidative stress indexes,such as total superoxide dismutase(SOD)and malondialdehyde,were detected(MDA,IL-6 and cTnI were measured.Results:compared with the blank group,the ECG of the model group changed significantly(P<0.01),the cTnI value increased significantly(P<0.01),indicating that the rat myocardial ischemia model was successfully established;compared with the model group,the SOD level of lidocaine group and lidocaine+sinomenine group increased significantly(P<0.05,P<0.01),the MDA level decreased significantly(P<0.05,P<0.01),IL-6 decreased significantly(P<0.05,P<0.01)05,P<0.01).Conclusion:sinomenine SGB has protective effect on rats with chronic myocardial ischemia,which is related to anti oxidative stress and inhibition of inflammatory reaction.展开更多
Sinomenine,a major active ingredient from traditional Chinese medicine Qingfengteng(Sinomenium acutum(Thunb.)Rehd.et Wils.),has been proven to have anti-inflammatory,analgesic,anti-tumor,immunomodulatory and other pha...Sinomenine,a major active ingredient from traditional Chinese medicine Qingfengteng(Sinomenium acutum(Thunb.)Rehd.et Wils.),has been proven to have anti-inflammatory,analgesic,anti-tumor,immunomodulatory and other pharmacological effects,and is clinically used for various inflammatory and autoimmune diseases.However,due to complex molecular mechanisms and pathological characteristics in inflammatory and immune responses,the precise anti-inflammatory and immunological mechanisms of sinomenine are still unclear.This review summarizes the anti-inflammatory and immunoregulatory mechanisms of sinomenine during recent years in rheumatoid arthritis,respiratory system,nervous system,digestive system and organ transplant rejection.The molecular pharmacological mechanisms of sinomenine responsible for anti-inflammatory and immunosuppressive effects were in detail introduced based on 3 aspects including cytokines induction,signal pathways modulation and immune cells function regulation.Moreover,this review also raises some concerns and challenges in future sinomenine study,which will contribute to crucial theoretical and practical significance for in-depth development and utilization of sinomenine as medicinal resource.展开更多
BACKGROUND Immature dendritic cells(imDCs)play an important role in the induction of donor-specific transplant immunotolerance.However,these cells have limitations,such as rapid maturation and a short lifespan in vivo...BACKGROUND Immature dendritic cells(imDCs)play an important role in the induction of donor-specific transplant immunotolerance.However,these cells have limitations,such as rapid maturation and a short lifespan in vivo.In previous studies,induced pluripotent stem cells(iPSCs)differentiated into imDCs,and sinomenine(SN)was used to inhibit the maturation of imDCs.AIM To study the capacity of SN to maintain iPSC-derived imDCs(SN-iPSCs-imDCs)in an immature state and the mechanism by which SN-iPSCs-imDCs induce immunotolerance.METHODS In this study,mouse iPSCs were induced to differentiate into imDCs in culture medium without or with SN(iPSCs-imDCs and SN-iPSCs-imDCs).The imDCrelated surface markers,endocytotic capacity of fluorescein isothiocyanate Dextran and apoptosis were analyzed by flow cytometry.The effects of iPSCs-imDCs and SNiPSCs-imDCs on T-cell stimulatory function,and regulatory T(Treg)cell proliferative function in vitro were analyzed by mixed lymphocyte reaction.Cytokine expression was detected by ELISA.The apoptosis-related proteins of iPSCs-DCs and SN-iPSCs-DCs were analyzed by western blotting.The induced immunotolerance of SN-iPSCs-DCs was evaluated by treating recipient Balb/c skin graft mice.Statistical evaluation of graft survival was performed using Kaplan–Meier curves.RESULTS Both iPSCs-imDCs and SN-iPSCs-imDCs were successfully obtained,and their biological characteristics and ability to induce immunotolerance were compared.SN-iPSCs-imDCs exhibited higher CD11c levels and lower CD80 and CD86 levels compared with iPSCs-imDCs.Reduced major histocompatibility complex II expression,worse T-cell stimulatory function,higher Treg cell proliferative function and stronger endocytotic capacity were observed with SN-iPSCs-imDCs(P<0.05).The levels of interleukin(IL)-2,IL-12,interferon-γin SN-iPSCs-imDCs were lower than those in iPSCs-imDCs,whereas IL-10 and transforming growth factor-βlevels were higher(P<0.05).The apoptosis rate of these cells was significantly higher(P<0.05),and the expression levels of cleaved caspase3,Bax and cleaved poly(ADP-ribose)polymerase were higher after treatment with lipopolysaccharides,but Bcl-2 was reduced.In Balb/c mice recipients immunized with iPSCsimDCs or SN-iPSCs-imDCs 7 d before skin grafting,the SN-iPSCs-imDCs group showed lower ability to inhibit donor-specific CD4+T-cell proliferation(P<0.05)and a higher capacity to induce CD4+CD25+FoxP3+Treg cell proliferation in the spleen(P<0.05).The survival span of C57bl/6 skin grafts was significantly prolonged in immunized Balb/c recipients with a donor-specific pattern.CONCLUSION This study demonstrated that SN-iPSCs-imDCs have potential applications in vitro and in vivo for induction of immunotolerance following organ transplantation.展开更多
Continuous manufacturing is considered as one of the future trends of pharmaceutical engineering. In this work, continuous liquid-liquid extraction for sinomenine purification was realized with the usage of centrifuga...Continuous manufacturing is considered as one of the future trends of pharmaceutical engineering. In this work, continuous liquid-liquid extraction for sinomenine purification was realized with the usage of centrifugal extractors. Chloroform was used as the extractant because of the high distribution coefficient (>100). Higher extraction ratio can be obtained when using the centrifugal extractor of Model CWL50-N. The extraction ratio of the second-stage extraction was higher than that of the first-stage extraction. The extraction ratio of the second-stage countercurrent extraction was higher than that of second-stage cross-flow extraction. When chloroform phase was recycled for liquid-liquid extraction, the extraction ratio was also higher than 95%. This work can also be an example of continuous liquid-liquid extraction for the separation of other Chinese medicine components.展开更多
Sinomenine(SIN) is a bioactive alkaloid compound extracted from a Chinese medicinal plant Sinomenium acutum. It is a multitarget antitumor natural substance. Various mechanisms have been proposed for the antitumor eff...Sinomenine(SIN) is a bioactive alkaloid compound extracted from a Chinese medicinal plant Sinomenium acutum. It is a multitarget antitumor natural substance. Various mechanisms have been proposed for the antitumor effects of SIN, such as direct cytotoxicity, induction of apoptosis, sensitization attenuating radiotherapy and chemotherapy, reversal of drug resistance, resistance to distant metastasis, and antiangiogenesis. SIN can be used as a tumor cell killer and an adjuvant to radiotherapy and chemotherapy. However, recent studies are mostly limited to the basic experimental stage; no systematic clinical studies have yet been reported. Therefore, this paper aimed to review the mechanism underlying the antitumor effects of SIN by consulting relevant domestic and foreign studies and to provide a relevant reference for further development, use, and exploration of SIN.展开更多
OBJECTIVE: To systematically evaluate the curative clinical efficacy and safety of sinomenine(SIN) in treatment of rheumatoid arthritis(RA) in comparison to methotrexate(MTX).METHODS: We searched the China National Kn...OBJECTIVE: To systematically evaluate the curative clinical efficacy and safety of sinomenine(SIN) in treatment of rheumatoid arthritis(RA) in comparison to methotrexate(MTX).METHODS: We searched the China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, Pubmed and Cochrane Library electronically up to August 31,2015, without language limitation. Only randomized controlled trials(RCTs) were included. Software Review Manager 5.3 was used for Meta-analysis.RESULTS: A total of 16 eligible studies within 1500RA patients were included. The meta-analysis indicated that on basis of MTX, SIN was more effective in total effective rate(P < 0.000 01). Besides, SIN alone versus MTX also showed advantages in RA therapy(P = 0.04) Taken together, adverse events occurred less frequently in combination of SIN and MTX than MTX alone(P < 0.0001), especially in digestive system(P < 0.000 01),while occurred more in dermato mucosal system with SIN treatment versus MTX(P = 0.02), and were similar for both remedies in nervous system(P = 0.12) and hematological system(P = 0.25).CONCLUTION: Compared to MTX, SIN had better clinical efficacy and relatively fewer adverse events in treatment of RA, especially when it was used together with MTX. Due to the poor methodological quality, well-designed, multiple-center RCTs are still required to further confirm the findings.展开更多
Objective: Premature and ill neonates undergo painful but medically necessary procedures while hospitalized. Although opiate drugs are administered as analgesics, problems associated with their side effects,tolerance,...Objective: Premature and ill neonates undergo painful but medically necessary procedures while hospitalized. Although opiate drugs are administered as analgesics, problems associated with their side effects,tolerance, and potential dependence necessitate research into alternative pain-relieving medications.Here we test two plant-derived compounds in infant rats: sinomenine, which targets the Mas-related G-protein-coupled receptor member X2 opioid receptor;and salvinorin A, which is a j opioid receptor agonist. In adult animals both sinomenine and salvinorin A are analgesic, but neither has been tested in infants.Methods: We used the formalin and thermal plantar tests in rats 7 and 21 days of age(PN7 and PN21) for behavioral signs of pain. In addition, brain sections were stained using Fos immunohistochemistry to examine patterns of brain activation in the midbrain periaqueductal gray and the paraventricular nucleus of the hypothalamus.Results: Sinomenine was analgesic in both the formalin and thermal tests on animals 21 days of age. At PN7 only the highest dose elevated response latencies in the thermal test and there were no effects of sinomenine in the formalin test. Analysis of Fos expression in the sinomenine-treated animals showed no drug effect, in contrast to the behavioral results. Salvinorin A was analgesic in the formalin test only at the highest dose at 21 days of age but not in the thermal test at either age.Conclusion: The increased modest effectiveness of sinomenine in older animals and the minimum salvinorin A drug effect suggest that the compounds act on sites that develop during the preweaning period(sinomenine) or after weaning(salvinorin A).展开更多
Objective:We evaluated the efficacy and safety of transdermal preparations of Sinomenium acutum(SA)for rheumatoid arthritis(RA).Methods:Randomized controlled trials(RCTs)of SA transdermal preparations for RA were extr...Objective:We evaluated the efficacy and safety of transdermal preparations of Sinomenium acutum(SA)for rheumatoid arthritis(RA).Methods:Randomized controlled trials(RCTs)of SA transdermal preparations for RA were extracted from relevant databases and screened in accordance with the inclusion criteria.The Cochrane System Evaluation Manual(version 5.1.0)was used to assess the quality of the included trials.We used the Cochrane Review Manager(version 5.4)to conduct the meta-analysis.Results:Six trials comprising 436 patients(220 patients in the treatment group and 216 patients in the control group)were analyzed.The meta-analysis indicated that SA transdermal preparations in combination with disease-modifying antirheumatic drugs(DMARDs)enhanced the overall effect(odds ratio[OR]3.97,95%confidence interval[CI][2.25,7.00],P<0.00001),decreased visual analogue scale(VAS)results(mean difference[MD]-0.64,95%CI[-1.20,-0.09],P=0.02),decreased laboratory indexes including the erythrocyte sedimentation rate(ESR)(MD-4.36,95%CI[-5.63,-3.08],P<0.00001)and C-reactive protein(CRP)(MD-3.6,95%CI[-3.99,-3.21,P<0.00001]),and decreased the Disease Activity Score-28(DAS28)(MD-0.41,95%CI[-0.78,-0.03],P=0.03).The results suggest that combination therapy did not shorten the duration of morning stiffness(DMS;standardized MD[SMD]-6.13,95%CI[-17.33,5.06],P=0.28)or reduce rheumatoid factor(RF)laboratory indexes(SMD-0.85;95%CI[-2.19,0.49],P=0.21).Only one study reported adverse reactions,and thus,it was difficult to determine whether adverse drug reactions in the combination therapy group were significantly different from those in the control group.Conclusion:We found that SA transdermal preparations combined with DMARDs may have greater clinical efficacy than DMARDs for RA.More well-designed and high-quality RCTs are required to verify the findings and determine whether transder-mal preparations cause fewer adverse events.展开更多
基金financially supported by the National Natural Science Foundation of China ( 21307028)Foundation of Henan province (202102310614)+1 种基金the Fundamental Research Funds for the Universities of Henan Province (NSFRF210428)the Foundation of Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University (KJS2016)。
文摘Sinomenine is the main bio-active ingredient of Sinomenii Caulis and usually produced by solventextraction techniques. However, the extraction of sinomenine suffers from the lack of highly efficient and environmentally-benign solvents. In this work, deep eutectic solvents(DESs) based on fragrances were synthesized, hydrogen-bond donors(HBDs) and hydrogen-bond acceptors(HBAs) components of DESs were identified and their extraction ability for sinomenine was evaluated and the extraction conditions were optimized by single-factor and orthogonal design experiments. It was found that the hydrogen-bonding interaction between sinomenine and DESs was the main extraction driving force and there was no explicit relationship between the extraction ability and the hydrophobicity of the DESs. The DESs could be recycled and sinomenine could be recovered quantitatively via backextraction. High-purity sinomenine((95.0 ± 2.3)%) could be produced. These findings suggest that DESs are highly-effective solvents for the isolation of sinomenine and exhibit great potential for the extraction of other bio-active compounds.
基金supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202002)the National Project for Standardization of Chinese Materia Medica (ZYBZH-C-GD-04)。
文摘Sinomenine hydrochloride is generally produced from Caulis Sinomenii. At present, the purification process in industrial production suffers from large amount of solid waste, high solvent toxicity, and low sinomenine hydrochloride yield. In this study, a new purification process for sinomenine hydrochloride was proposed by using the extract obtained from acid extraction of Caulis Sinomenii as the starting material.The process included the following steps: alkalization, extraction, water washing, acid–water stripping,drying, and crystallization. 1-Heptanol was used as the extractant. The distribution coefficients of sinomenine and sinomenine hydrochloride in 1-heptanol–water system were 27.4 and 0.0167, respectively.The dissociation constants of sinomenine hydrochloride were 8.27 and 11.24, respectively. Process parameters of the new purification process were optimized with experimental design. The extractant1-heptanol and sinomenine hydrochloride in the crystallization mother solution can be recycled in the new process. The purity of the obtained sinomenine hydrochloride crystals exceeded 85%, and the yield was about 70%. Compared with current industrial processes, safer extractant, less solid waste, and higher sinomenine hydrochloride yield can be achieved using the new purification process of sinomenine hydrochloride provided in this study.
文摘AIM:To investigate the inhibitory effects of sinomenine(SIN)combined with 5-fluorouracil(5-FU)on esophageal carcinoma in vitro and in vivo.METHODS:Esophageal carcinoma(Eca-109)cells were cultured in DMEM.The single or combined growth inhibition effects of SIN and 5-FU on the Eca-109 cells were examined by measuring the absorbance of CCK-8dye in living cells.Hoechst 33258 staining and an Annexin V/PI apoptosis kit were used to detect the percentage of cells undergoing apoptosis.Western blotting was used to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis.SIN at 25mg/kg and 5-FU at 12 mg/kg every 3 d,either combined or alone,was injected into nude mice and tumor growth inhibition and side effects of the drug treatment were observed.RESULTS:SIN and 5-FU,both in combination and individually,significantly inhibited the proliferation of Eca-109 cells and induced obvious apoptosis.Furthermore,the combined effects were greater than those of the individual agents(P<0.05).Annexin V/PI staining and Hoechst 33258 staining both indicated that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone were significantly different from the control(P<0.05).The up-regulation of Bax and downregulation of Bcl-2 showed that the essential mechanism of apoptosis induced by SIN and 5-FU occurs via the mitochondrial pathway.SIN and 5-FU alone significantly inhibited the growth of tumor xenografts in vivo,and the combined inhibition rate was even higher(P<0.05).During the course of chemotherapy,no obvious side effects were observed in the liver or kidneys.CONCLUSION:The combined effects of SIN and 5-FU on esophageal carcinoma were superior to those of the individual compounds,and the drug combination did not increase the side effects of chemotherapy.
基金supported by Science Fund of the Health Department of Jiangsu Province (No. H200504)
文摘Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum.It is widely used as an immunosuppressive drug for treating rheumatic and arthritic diseases.In our previous studies,we found that sinomenine reduced cellular infiltration within the spinal cord and alleviated experimental autoimmune encephalomyelitis(EAE) in rats.In this study,we further investigated the mechanisms of sinomenine treatment in EAE rats.In EAE rats,treatment with sinomenine exerted an anti-inducible NO synthase(anti-iNOS) effect,which is related to the reductions of Th1 cytokine interferon-γ(IFN-γ) and its transcription factor,T-bet,in spinal cords.Moreover,sinomenine treatment of splenocytes stimulated with anti-CD3 antibody and recombinant rat interleukin 12 reduced the expression of T-bet and IFN-γ in vitro and also reduced the capability of supernatants of splenocyte culture to induce iNOS expression by primary astrocytes.However,sinomenine had no direct inhibitory effect on iNOS produced by astrocytes cultured with IFN-γ and tumor necrosis factor α in vitro.In conclusion,the anti-iNOS effect of sinomenine on EAE is mediated via the suppression of T-bet /IFN-γ pathway.
文摘Sinomenine(SN)has been used in the clinical treatment of systemic lupus erythematosus and rheumatoid arthritis for many years.Studies showed that SN held protective effects such as anti-inflammation,scavenging free radicals and suppressing immune response in many autoimmune diseases.The purpose of the present study is to explore the mechanism of anti-inflammation of SN on lipopolysaccharide(LPS)-induced macrophages activation and investigate whether the TLR4/NF-κB signaling pathway participated in.Macrophages isolated from mouse peritoneal cavity were stimulated by 1 pg/mL LPS for 24 h.And then the cells were treated with various concentrations of SN,TLR4 inhibitor respectively for additional 48 h.Drug toxicity was detected by MTT assay and Transwell experiment was used to assess chemotaxis.Furthermore,TLR4 and MyD88 mRNA levels were detected by real-time PCR.Western blotting was used to examine TLR4,MyD88 and phosphorylated IκB protein expression in macrophages.Immunofluorescence assay was applied to observe p65 NF-κB protein expression in macrophage nucleus.We extracted macrophages with high purity and activity from the abdominal cavity of mice.SN remarkably inhibited the chemotaxis and secretion function of LPS-stimulated macrophages.It also down-regulated both the protein levels of inflammatory cytokines(TNF-α,IL-β and IL-6)and the RNA and protein levels of the key factors(TLR4,MyD88,p-IkB)in TLR4 pathway.The expression of p65 NF-κB protein in nuclei was down-regulated,which was correlated with a similar decrease in p-IκB protein level.In conclusion,SN can inhibit the LPS induced immune responses in macrophages by blocking the activated TLR4/NF-κB signaling pathway.These results may provide a therapeutic approach to regulate inflammatory responses.
文摘The effect of Sinomenine on IL-8, IL-6, IL-2 and mIL-2R produced by peripheral blood mononuclear cells was investigated by using cell culture, radioimmunoassay and flow cytometry. It was showed that production of IL-8 and mIL-2R was inhibited, but the levels of IL-6 were enhanced by Sinomenine. Our results also demonstrated that Sinomenine did not have any effect on the production of IL-2. The study demonstrated that Sinomenine was able to regulate the production of cytokines. This may be one of the mechanisms by which Sinomenine works on rheumatoid arthritis.
基金financially supported by grants from the Macao Science and Technology Development Fund(0032/2018/AFJ,0003/2019/AKP,and 0010/2020/A1)the Key Program in Emerging Industry of the Hunan Department of Science&Technology(2014GK1058)funded by Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery(001/2020/ALC)supported by the Macao Science and Technology Development Fund。
文摘Sinomenine(SIN)is commonly used as part of rheumatoid arthritis(RA)therapy in China,but there is still no published evidence of the efficacy of SIN monotherapy.This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients.In this 24 week,randomized,placebo-controlled,double-blind clinical trial,people with mild to moderate RA were randomly assigned(1:1:1,stratified by hospital)to receive SIN(120 mg,twice daily),methotrexate(MTX)(10 mg per week),or SIN+MTX therapy.The primary outcome was the proportion of patients who achieved a 50%improvement in the American College of Rheumatology(ACR50)criteria at week 24 and who showed improvement according to the clinical disease activity index(CDAI).In this prospective subgroup analysis,we also assessed whether the 24-week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine.Of the 135 enrolled participants,38,39,and 36 patients were treated with SIN,MTX,and SIN+MTX,respectively.In the SIN-treated group,52.63%of patients achieved ACR50 after 24-weeks of treatment,which was comparable to the results in the MTX-treated and SIN+MTX-treated groups.Hepatic and gastrointestinal disorders were the main adverse events;however,the ratio of patients suffering from hepatic disorder in the SIN group(1/38)was much lower than that in the MTX(10/39)and SIN+MTX(8/36)groups.A total of 221 serum samples were collected at the four follow-up time points in the three treatments,and the levels of ornithine,citrulline,and arginine were obtained through ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF/MS).The serum ornithine level decreased after the 24-week treatment along with a decrease in disease activity,and may reflect therapeutic responses with a sensitivity value of 80%.In conclusion,SIN revealed a comparable efficacy to MTX for treating RA patients,but with fewer side effects.In addition,the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA,which shows the value of this measure as an assessment indicator of drugs in treating RA.
文摘BACKGROUND Rheumatoid arthritis(RA)is a prevalent clinical autoimmune disease that is commonly treated with diclofenac and methotrexate.In recent years,the application of traditional Chinese medicine in RA has received widespread attention;it promotes blood circulation,strengthens the immune system,and eliminates evil.The sinomenine preparation of Zhingqeng Fengtongning is studied as a possible treatment for patients with RA.AIM To explore the value of sinomenine injection into the articular cavity for the treatment of RA.METHODS A total of 94 patients with RA treated from January 2019 to January 2021 were selected and divided into the study and control groups with 47 patients each using a simple random number table method.Both groups received conventional treatment with diclofenac sodium and methotrexate tablets.The control group received diproxone and lidocaine by intra-articular administration while the study group received an intra-articular administration of the sinomenine preparation of Zhengqing Fengning and lidocaine.χ^(2) test was used to evaluate the therapeutic effect and synovial thickness,degree of pain through the visual analog scale(VAS),blood flow grade,arthroinflammatory indexes[rheumatoid factor(RF),C-reactive protein(CRP),and erythrocyte sedimentation rate(ESR)]before and after treatment in the two groups.RESULTS The total effective rate of the study group(93.62%)was higher than that of the control group(78.72%)(P<0.05).Before treatment,there were no significant differences between the two groups in terms of synovial thickness,VAS score,blood flow grading,levels of RF,and ESR(P>0.05).After treatment,the synovial thickness and VAS score were significantly lower(P<0.05)in the study group than in the control group(2.05±0.59 mm vs 2.87±0.64 mm and 2.11±0.62 vs 2.90±0.79 scores,respectively).The rate of blood flow at grade 0 in the study group(76.60%)was higher than that in the control group(57.45%),and the rate of blood flow at grade I(10.64%)was lower than that in the control group(31.91%)(P<0.05).Furthermore,the levels of RF(55.61±6.13 U/mL),CRP(11.43±3.59 mg/L),and ESR(29.60±5.56 mm/h)in the study group were lower than those in the control group(73.04±9.23 U/mL,15.07±4.06 mg/L,36.64±6.10 mm/h,respectively)(P<0.05).CONCLUSION Sinomenine administration of Zhengqing Fengtongning in the articular cavity with conventional treatment of RA can improve ultrasonographic blood flow and synovial thickness,reduce pain,regulate inflammation,and enhance therapeutic effect.
基金National Administration of traditional Chinese medicine base project(No.jdzx2012144,jdzx2015253)Shaanxi provincial major disease TCM innovation plan:chest obstruction(coronary heart disease)+1 种基金Shaanxi Provincial Administration of traditional Chinese medicine scientific research project(No.15-scjh015,15-lc016,lcpt089,15-scjh016)discipline innovation team of the Second Affiliated Hospital of Shaanxi University of Chinese medicine(No.2020xktd-b03)。
文摘Objective:To investigate the protective effect of sinomenine stellate ganglion block(SGB)on chronic myocardial ischemia and its related mechanism.Methods:SD male and female rats(180~200g)were randomly divided into four groups:blank group,model group,lidocaine group,lidocaine+sinomenine group.The rats in blank group were fed with normal standard diet without modeling,and the other rats were fed with high-fat diet.After 8 weeks of feeding,the rats in high-fat diet group were significantly different from those in blank control group.Then they were randomly divided into 3 groups,10 rats in model group were injected with 0.9%NaCl into right stellate ganglion(RSG)After 2 weeks of continuous injection,pituitrin injection was continuously injected into sublingual vein of rats for 3 days,once every 24 hours;lidocaine group rats were injected with 0.24 mL 1%lidocaine injection in RSG,the rest was the same as model group;lidocaine+sinomenine group rats were injected with 0.24 mL 1%lidocaine injection+0.095 mL sinomenine hydrochloride+2.9 mL 0.8 mL 0.8 mL in RSG,the rest was the same as model group.At the end of the eighth week of the experiment,the rats in the high-fat diet feeding group and the standard ordinary diet feeding group were given the medicine after there was significant difference in blood lipid;before the third injection of pituitrin,the ECG changes of the rats in each group were observed;the general situation of the rats before and after the administration was observed;after the experiment,the blood of the rats in each group was taken from the abdominal aorta,and the serum oxidative stress indexes,such as total superoxide dismutase(SOD)and malondialdehyde,were detected(MDA,IL-6 and cTnI were measured.Results:compared with the blank group,the ECG of the model group changed significantly(P<0.01),the cTnI value increased significantly(P<0.01),indicating that the rat myocardial ischemia model was successfully established;compared with the model group,the SOD level of lidocaine group and lidocaine+sinomenine group increased significantly(P<0.05,P<0.01),the MDA level decreased significantly(P<0.05,P<0.01),IL-6 decreased significantly(P<0.05,P<0.01)05,P<0.01).Conclusion:sinomenine SGB has protective effect on rats with chronic myocardial ischemia,which is related to anti oxidative stress and inhibition of inflammatory reaction.
基金This research was funded by National Natural Science Foundation of China(No.81973505)The National Key Research and Development Program of China(No.2019YFC1708902,2019YFC1711000).
文摘Sinomenine,a major active ingredient from traditional Chinese medicine Qingfengteng(Sinomenium acutum(Thunb.)Rehd.et Wils.),has been proven to have anti-inflammatory,analgesic,anti-tumor,immunomodulatory and other pharmacological effects,and is clinically used for various inflammatory and autoimmune diseases.However,due to complex molecular mechanisms and pathological characteristics in inflammatory and immune responses,the precise anti-inflammatory and immunological mechanisms of sinomenine are still unclear.This review summarizes the anti-inflammatory and immunoregulatory mechanisms of sinomenine during recent years in rheumatoid arthritis,respiratory system,nervous system,digestive system and organ transplant rejection.The molecular pharmacological mechanisms of sinomenine responsible for anti-inflammatory and immunosuppressive effects were in detail introduced based on 3 aspects including cytokines induction,signal pathways modulation and immune cells function regulation.Moreover,this review also raises some concerns and challenges in future sinomenine study,which will contribute to crucial theoretical and practical significance for in-depth development and utilization of sinomenine as medicinal resource.
基金Supported by National Natural Science Foundation of China,No.81900686Science and Technology Incubation Fund Project of Shaanxi Provincial People’s Hospital,No.2020YXM-08+2 种基金Technology Talent Support Program of Shaanxi Provincial People’s Hospital,No.2021BJ-07Key Projects of Shaanxi Provincial Department of Education,No.21JS038Medical Research Development Fund of Beijing Kangmeng Charity Foundation,No.7B202010.
文摘BACKGROUND Immature dendritic cells(imDCs)play an important role in the induction of donor-specific transplant immunotolerance.However,these cells have limitations,such as rapid maturation and a short lifespan in vivo.In previous studies,induced pluripotent stem cells(iPSCs)differentiated into imDCs,and sinomenine(SN)was used to inhibit the maturation of imDCs.AIM To study the capacity of SN to maintain iPSC-derived imDCs(SN-iPSCs-imDCs)in an immature state and the mechanism by which SN-iPSCs-imDCs induce immunotolerance.METHODS In this study,mouse iPSCs were induced to differentiate into imDCs in culture medium without or with SN(iPSCs-imDCs and SN-iPSCs-imDCs).The imDCrelated surface markers,endocytotic capacity of fluorescein isothiocyanate Dextran and apoptosis were analyzed by flow cytometry.The effects of iPSCs-imDCs and SNiPSCs-imDCs on T-cell stimulatory function,and regulatory T(Treg)cell proliferative function in vitro were analyzed by mixed lymphocyte reaction.Cytokine expression was detected by ELISA.The apoptosis-related proteins of iPSCs-DCs and SN-iPSCs-DCs were analyzed by western blotting.The induced immunotolerance of SN-iPSCs-DCs was evaluated by treating recipient Balb/c skin graft mice.Statistical evaluation of graft survival was performed using Kaplan–Meier curves.RESULTS Both iPSCs-imDCs and SN-iPSCs-imDCs were successfully obtained,and their biological characteristics and ability to induce immunotolerance were compared.SN-iPSCs-imDCs exhibited higher CD11c levels and lower CD80 and CD86 levels compared with iPSCs-imDCs.Reduced major histocompatibility complex II expression,worse T-cell stimulatory function,higher Treg cell proliferative function and stronger endocytotic capacity were observed with SN-iPSCs-imDCs(P<0.05).The levels of interleukin(IL)-2,IL-12,interferon-γin SN-iPSCs-imDCs were lower than those in iPSCs-imDCs,whereas IL-10 and transforming growth factor-βlevels were higher(P<0.05).The apoptosis rate of these cells was significantly higher(P<0.05),and the expression levels of cleaved caspase3,Bax and cleaved poly(ADP-ribose)polymerase were higher after treatment with lipopolysaccharides,but Bcl-2 was reduced.In Balb/c mice recipients immunized with iPSCsimDCs or SN-iPSCs-imDCs 7 d before skin grafting,the SN-iPSCs-imDCs group showed lower ability to inhibit donor-specific CD4+T-cell proliferation(P<0.05)and a higher capacity to induce CD4+CD25+FoxP3+Treg cell proliferation in the spleen(P<0.05).The survival span of C57bl/6 skin grafts was significantly prolonged in immunized Balb/c recipients with a donor-specific pattern.CONCLUSION This study demonstrated that SN-iPSCs-imDCs have potential applications in vitro and in vivo for induction of immunotolerance following organ transplantation.
文摘Continuous manufacturing is considered as one of the future trends of pharmaceutical engineering. In this work, continuous liquid-liquid extraction for sinomenine purification was realized with the usage of centrifugal extractors. Chloroform was used as the extractant because of the high distribution coefficient (>100). Higher extraction ratio can be obtained when using the centrifugal extractor of Model CWL50-N. The extraction ratio of the second-stage extraction was higher than that of the first-stage extraction. The extraction ratio of the second-stage countercurrent extraction was higher than that of second-stage cross-flow extraction. When chloroform phase was recycled for liquid-liquid extraction, the extraction ratio was also higher than 95%. This work can also be an example of continuous liquid-liquid extraction for the separation of other Chinese medicine components.
基金Supported by the Scientific Program of Traditional Chinese Medicine of Chongqing Health and Family Planning Commission(No.ZY201801010,ZY201802114)
文摘Sinomenine(SIN) is a bioactive alkaloid compound extracted from a Chinese medicinal plant Sinomenium acutum. It is a multitarget antitumor natural substance. Various mechanisms have been proposed for the antitumor effects of SIN, such as direct cytotoxicity, induction of apoptosis, sensitization attenuating radiotherapy and chemotherapy, reversal of drug resistance, resistance to distant metastasis, and antiangiogenesis. SIN can be used as a tumor cell killer and an adjuvant to radiotherapy and chemotherapy. However, recent studies are mostly limited to the basic experimental stage; no systematic clinical studies have yet been reported. Therefore, this paper aimed to review the mechanism underlying the antitumor effects of SIN by consulting relevant domestic and foreign studies and to provide a relevant reference for further development, use, and exploration of SIN.
基金Supported by National Natural Science Foundation of China(Based on VIP to Investigate the Mechanism of Lung-Intestines Combined Therapeutic Method in Treating Sjogren's Syndrome No.81473607)State Administration of Traditional Chinese Medicine Key Discipline Open Project(Bi-Syndrome of Traditional Chinese Medicine Science,No.BBXK2013101)
文摘OBJECTIVE: To systematically evaluate the curative clinical efficacy and safety of sinomenine(SIN) in treatment of rheumatoid arthritis(RA) in comparison to methotrexate(MTX).METHODS: We searched the China National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, Pubmed and Cochrane Library electronically up to August 31,2015, without language limitation. Only randomized controlled trials(RCTs) were included. Software Review Manager 5.3 was used for Meta-analysis.RESULTS: A total of 16 eligible studies within 1500RA patients were included. The meta-analysis indicated that on basis of MTX, SIN was more effective in total effective rate(P < 0.000 01). Besides, SIN alone versus MTX also showed advantages in RA therapy(P = 0.04) Taken together, adverse events occurred less frequently in combination of SIN and MTX than MTX alone(P < 0.0001), especially in digestive system(P < 0.000 01),while occurred more in dermato mucosal system with SIN treatment versus MTX(P = 0.02), and were similar for both remedies in nervous system(P = 0.12) and hematological system(P = 0.25).CONCLUTION: Compared to MTX, SIN had better clinical efficacy and relatively fewer adverse events in treatment of RA, especially when it was used together with MTX. Due to the poor methodological quality, well-designed, multiple-center RCTs are still required to further confirm the findings.
基金supported in part by the Department of Anesthesiology and Critical Care at the Children’s Hospital of Philadelphia,the James Battaglia Endowed Chair to G.A.Barra Faculty Mentoring Undergraduate Research grant to C.J.Mascarenhas and G.A.Barr+1 种基金supported by National Institutes of Health Grant R01(1R01GM111421)the Department of Anesthesiology and Critical Care at the University of Pennsylvania.
文摘Objective: Premature and ill neonates undergo painful but medically necessary procedures while hospitalized. Although opiate drugs are administered as analgesics, problems associated with their side effects,tolerance, and potential dependence necessitate research into alternative pain-relieving medications.Here we test two plant-derived compounds in infant rats: sinomenine, which targets the Mas-related G-protein-coupled receptor member X2 opioid receptor;and salvinorin A, which is a j opioid receptor agonist. In adult animals both sinomenine and salvinorin A are analgesic, but neither has been tested in infants.Methods: We used the formalin and thermal plantar tests in rats 7 and 21 days of age(PN7 and PN21) for behavioral signs of pain. In addition, brain sections were stained using Fos immunohistochemistry to examine patterns of brain activation in the midbrain periaqueductal gray and the paraventricular nucleus of the hypothalamus.Results: Sinomenine was analgesic in both the formalin and thermal tests on animals 21 days of age. At PN7 only the highest dose elevated response latencies in the thermal test and there were no effects of sinomenine in the formalin test. Analysis of Fos expression in the sinomenine-treated animals showed no drug effect, in contrast to the behavioral results. Salvinorin A was analgesic in the formalin test only at the highest dose at 21 days of age but not in the thermal test at either age.Conclusion: The increased modest effectiveness of sinomenine in older animals and the minimum salvinorin A drug effect suggest that the compounds act on sites that develop during the preweaning period(sinomenine) or after weaning(salvinorin A).
基金The study was financed by the Financing Scheme of Arising Interdisciplinary Subject of TCM in Shanghai,China(No.Shxxjcxk201709)the TCM Genre Program of Shanghai Health Bureau of China(No.ZY(2018-2020)-CCCX1006)the Shanghai Sports Bureau Project of China(Nos.20J020 and 21J013).
文摘Objective:We evaluated the efficacy and safety of transdermal preparations of Sinomenium acutum(SA)for rheumatoid arthritis(RA).Methods:Randomized controlled trials(RCTs)of SA transdermal preparations for RA were extracted from relevant databases and screened in accordance with the inclusion criteria.The Cochrane System Evaluation Manual(version 5.1.0)was used to assess the quality of the included trials.We used the Cochrane Review Manager(version 5.4)to conduct the meta-analysis.Results:Six trials comprising 436 patients(220 patients in the treatment group and 216 patients in the control group)were analyzed.The meta-analysis indicated that SA transdermal preparations in combination with disease-modifying antirheumatic drugs(DMARDs)enhanced the overall effect(odds ratio[OR]3.97,95%confidence interval[CI][2.25,7.00],P<0.00001),decreased visual analogue scale(VAS)results(mean difference[MD]-0.64,95%CI[-1.20,-0.09],P=0.02),decreased laboratory indexes including the erythrocyte sedimentation rate(ESR)(MD-4.36,95%CI[-5.63,-3.08],P<0.00001)and C-reactive protein(CRP)(MD-3.6,95%CI[-3.99,-3.21,P<0.00001]),and decreased the Disease Activity Score-28(DAS28)(MD-0.41,95%CI[-0.78,-0.03],P=0.03).The results suggest that combination therapy did not shorten the duration of morning stiffness(DMS;standardized MD[SMD]-6.13,95%CI[-17.33,5.06],P=0.28)or reduce rheumatoid factor(RF)laboratory indexes(SMD-0.85;95%CI[-2.19,0.49],P=0.21).Only one study reported adverse reactions,and thus,it was difficult to determine whether adverse drug reactions in the combination therapy group were significantly different from those in the control group.Conclusion:We found that SA transdermal preparations combined with DMARDs may have greater clinical efficacy than DMARDs for RA.More well-designed and high-quality RCTs are required to verify the findings and determine whether transder-mal preparations cause fewer adverse events.
