Is"Pangolin(Manis Squama)is not used in medicine"an improvement in the protection of precious and rare species or an improvement in the safety of using medicine?

Recently,a number of reports about pangolin have become hot news:The Chinese Pharmacopoeia(2020 edition)has not continued to include the drug-using standards for pangolin(Manis Squama),aristolochic(Aristolochia debilis Sieb.et Zucc),celestial vine(Fibraurea recisa Pierre),and Chinese patent drug Huanglian Yanggan pills(approval number by China State Food and Drug Administration:Z200113194).On June 5,2020,the China Forestry Administration Bureau and the Grassland Bureau co-issued an announcement to upgrade all the species of genus pangolins from the national second level of the protected wildlife to the first level.The new coronavirus(SARS-CoV-2)is also highly similar to the beta coronavirus isolated from pangolin[1].

Pretreatment with Lithospermic Acid Attenuates Oxidative Stress-induced Apoptosis in Bone Marrow-derived Mesenchymal Stem Cells via Anti-oxidation and Activation of PI3K/Akt Pathway

Objective Despite the potential therapeutic approaches of bone marrow-derived mesenchymal stem cells(BMSCs)in orthopaedic,their applications are hampered by harsh oxidative stress conditions after transplantation.In this study,the antiapoptotic and anti-oxidative properties of lithospermic acid(LSA)on BMSCs exposed to hydrogen peroxide(H2O2)were investigated.Methods In the present study,we used H2O2 to induce oxidative injury on BMSCs.Reactive oxygen species(ROS)staining and superoxide dismutase(SOD)assay were performed.The expression levels of phosphorylated(p)-Akt,Bcl-2-associated X protein(Bax)and B-cell lymphoma 2(Bcl-2)were measured by Western blotting.Results LSA can significantly reduce H2O2-induced chromatin condensation and intracellular ROS levels,enhance the activity of SOD.Moreover,it can alleviate H2O2-induced apoptosis by upregulating Bcl-2 and p-Akt,down-regulating Bax,which was blocked by the PI3K inhibitor,LY294002.Conclusions Our results demonstrated that pretreatment with LSA could attenuate oxidative stress-induced apoptosis in BMSCs,which may be related with anti-oxidant properties and partly via modulating PI3K/Akt pathway,suggesting that pharmacologically manipulating BMSCs with LSA could be a promising drug to increase cell survival for BMSCs transplantation in musculoskeletal disorders of orthopaedic.

Network pharmacology and molecular docking analysis on molecular targets and mechanism prediction of Huanglian Jiedu Decoction in the treatment of COVID-19

Objective To investigate and predict the molecular targets and mechanism of Huanglian Jiedu Decoction(黄连解毒汤,HLJDD)in the treatment of Corona Virus Disease 2019(COV-ID-19)through network pharmacology and molecular docking analysis.Methods The chemical constituents and action targets of HLJDD were retrieved on Tradi-tional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),SymMap v2,Encyclopedia of Traditional Chinese Medicine(ETCM),a High-throughput Ex-periment-and Reference-guided Database of Traditional Chinese Medicine(HERB),and Tra-ditional Chinese Medicine Integrated Database(TCMID).UniProt and GeneCards were used to query the target genes that corresponding to the active compounds,and then a compound-target network was constructed using Cytoscape 3.7.2.Gene Ontology(GO)database was used to annotate GO functions.Kyoto Encyclopedia of Genes and Genomes(KEGG)was used to predict the possible mechanisms of active compounds.The Database for Annotation,Visu-alization and Integrated Discovery(DAVID)was used to analysis the tissue enrichment.The main active compounds in HLJDD are molecularly docked with their corresponding related targets.Results Seventy-six compounds were screened and 458 corresponding targets in the network were obtained.Gene annotation showed that the targets were involved mainly in 1953 biolo-gical processes.884 signaling pathways was enriched,involving signaling by interleukins,cy-tokine signaling in immune system,generic transcription pathway,and RNA polymerase II transcription.The targets mainly distributed in the lung,liver,and placenta,involving a vari-ety of immune cells,such as T cells and B cells.The molecular docking results showed that core compounds such as wogonin,berberine,and baicalein had high affinity with tumor nec-rosis factor(TNF),insulin(INS),and tumor protein 53(TP53).Conclusion The active compounds in HLJDD may have a therapeutic effect on COVID-19 through regulating multiple signal pathways by targeting genes such as vascular endothelial growth factor A(VEGFA),INS,interleukin-6(IL-6),TNF,caspase-3,TP53,and mitogen-activ-ated protein kinase 3(MAPK3).

Analysis of Zhang Xichun's Academic Thoughts of Using Shanzhuyu(Corni Fructus)

Zhang Xichun classifed the collapse syndrome into upper collapse,lower collapse and exterior col-lapse.Based on the therapeutic principle of tonifying the liver and astringing the liver to consolidate collapse,he used drugs boldly to cure disease.The method of tonifying the liver and astringing sweating is applied to res-cue exterior collapse with Laifu Deoction(来复汤);the method of tonifying the liver and relieving asthma is applied to treat upper collapse with Shenzhe Zhenqi Decoction(参赭镇气汤);the method of restoring yang with emergent treatment is applied to rescue the lower collapse with Jijiu Huiyang Decoction(急救回阳汤).This will provide references for the prevention and treatment of critical diseases for later generations in practi-cing Chinese medicine.

Mechanism of dihydrotanshinone I in the treatment of helicobacter pylori infection based on network pharmacology and molecular docking technology

Objective:Based on the network pharmacology approach and molecular docking technology,the core targets of dihydrotanshinone I(DHT)for the treatment of helicobacter pylori(Hp)infection were searched and the potential mechanisms of drug therapy were explored.Methods:The TCMSPdatabase and Swiss Target Prediction database were employed to identify drug targets.To mine disease targets based on GeneCards,OMIM,DrugBank,DisGeNET,and TTDdatabases.Then the two were intersected to obtain common targets.The proteinproteininteraction(PPI)networkmap of common targets was constructed on the basis of the String network platform and Cytoscape software,and the targets with degree values over 1/2 maximum degree value were selected as core targets.Molecular docking verification of DHTand core targets were performed using AutoDock and PyMOL software.Finally,gene ontology(GO)functional enrichment analysis andKyoto Encyclopediaof Genes and Genomes(KEGG)pathway enrichment analysis of the common targets were carried out using the Metascape database and R-4.0.2-win software.Results:A total of 13 targets of DHTwas extracted for the treatment of Hp,and five core targets,includingSignal transducerand activator of transcription 1(STAT1),Signal transducerand activator of transcription 3(STAT3),Prostaglandin G synthase 2(PTGS2),Signal transducerand activator of transcription 4(STAT4)and Indoleamine 2,3-dioxygenase 1(IDO1),were screened according to their degree values.Molecular docking indicated that DHThad an excellent binding to the core target.29 pathways were yielded by KEGG enrichment analysis,and a total of 48 biological processes,7 cellular components and 13 molecular functions were derived from GO enrichment analysis.Conclusion:DHTmay decrease pro-inflammatory factor expression and immune cell infiltration to treat Hpinfection via the janus kinase(JAK)-signal transducer and activator of transcription(STAT)signaling pathway regulated by STAT1,STAT3,STAT4,etc.

Naringin Inhibits Colorectal Carcinogenesis by Inhibiting Viability of Colorectal Cancer Cells

Objective To explore the therapeutic effect of naringin on colorectal cancer(CRC)and the related mechanism.Methods Cell counting kit-8(CCK-8)assay and annexin V-FITC/PI assay were used to detect the effect of naringin(50–400µg/mL)on cell proliferation and apoptosis of CRC cells,respectively.The scratch wound assay and transwell migration assay were used to assess the effect of naringin on CRC cell migration.Four-week-old male nude mice were injected with HCT116 cells subcutaneously to establish the tumor xenograft model.Naringin was injected intraperitoneally at 50 mg/(kg·d),with solvent and 5-fluorouracil treatment as control.The width and length of the tumors were measured and recorded every 6 days,and tumor tissues were photographed and weighed on the last day of the 24-d observation period.Immunohistochemical staining for caspase-3,proliferating cell nuclear antigen and TUNEL assay were used to evaluate the effect of naringin on cell proliferation and apoptosis in tumor tissues.The body weight,food and water intake of mice were recorded,and the major organs in different treatment groups were weighed on the last day and stained with hematoxylin and eosin for histological analysis.Meanwhile,the routine blood indicators were recorded.Results CCK-8 and annexin V-FITC/PI results confirmed that naringin(100,200,and 400µg/mL)could inhibit proliferation and promote apoptosis.The scratch wound assay and transwell migration assay results confirmed the inhibitory activity of naringin against CRC cells migration.In vivo results demonstrated the inhibitory effect of naringin on tumor growth with good bio-compatibility.Conclusion Naringin inhibited colorectal carcinogenesis by inhibiting viability of CRC cells.

Effect of acupuncture plus Tai Ji Quan on the recovery of neurological function and depression state in post-stroke depression patients

Objective：To observe the therapeutic efficacy of acupuncture plus Tai Ji Quan （Tai Chi） in recovering the neurological function and treating depression state in post-stroke depression patients,together with a 12-month follow-up.Methods：A total of 105 eligible post-stroke depression patients were randomized into an acupuncture plus Tai Ji group （53 cases） and a control group （52 cases） based on their visiting sequence.The patients all received routine treatment and rehabilitation training for stroke.In addition,the control group was given oral administration of citalopram hydrobromide tablets,1 month as a course of treatment,for 3 courses in total.Meanwhile,the acupuncture plus Tai Ji group received acupuncture and practiced Tai Ji Quan,for 1 month and 12 months respectively.Before the intervention,after 1-month intervention and 12 months later,the National Institute of Health stroke scale （NIHSS）,Barthel index （BI） and Hamilton depression rating scale （HAMD） were adopted for efficacy evaluation.Results：Prior to the intervention,there were no significant differences in HAMD,NIHSS and BI scores between the two groups （all P〉0.05）;after 1-month intervention,there were significant between-group differences in NIHSS,BI and HAMD scores （P〈0.05 or P〈0.01）;the 12-month follow-up revealed significant between-group differences in NIHSS,BI and HAMD scores （all P〈0.01）.In the treatment of stroke,the total effective rate was 84.4% in the acupuncture plus Tai Ji group,significantly higher than 68.9% in the control group （P〈0.05）;in the treatment of depression,the total effective rate was 86.7% in the acupuncture plus Tai Ji group,significantly higher than 77.8% in the control group （P〈0.05）.Conclusion：Acupuncture plus Tai Ji Quan can produce a significant efficacy in improving the limb motor function and depression in post-stroke depression patients.

Effect of combining acupuncture and auricular point sticking on heart rate variability in patients with post-stroke depression

Objective:To investigate the effect of combining acupuncture and auricular point sticking on heart rate variability(HRV)in patients with post-stroke depression(PSD).Methods:A total of 80 cases with PSD were randomized into a treatment group and a control group.The control group was intervened by oral administration of paroxetine hydrochloride,whereas the treatment group received acupuncture plus auricular point sticking base on the same oral administration.The Hamilton depression rating scale(HAMD)and HRV were measured before and after treatment in both groups.Results:The individual and global scores of HAMD significantly dropped after 8 weeks of treatment in both groups(all P〈0.05).In the treatment group,anxiety/somatization factor,sleep disturbance,hopelessness factor,cognition factor and global score were significantly different from those in the control group(all P〈0.05).The 24 h standard deviation of all normal-to-normal R-R interval(SDNN),standard deviation of 5-minute average of normal R-R intervals(SDANN),root mean square of successive differences(RMSSD),percent of differences between adjacent normal R-R intervals 50 ms(PNN50)and high frequency(HF)were increased while low frequency(LF)and LF/HF decreased significantly after 8 weeks of treatment in both groups(P〈0.05).All items in the treatment group were significantly different from those in the control group(all P〈0.05).Conclusion:Combining acupuncture and auricular point sticking can enhance the conventional medical treatment for HRV in patients with PSD.

Effect of herbal cake-partitioned moxibustion on Leptin/JAK#STAT3 in lipid-lowering pathway of hyperlipidemia rabbits

Objective:To observe the lipid-lowering effect of different transdermal absorption enhancers applied to the herbal cake-partitioned moxibustion in hyperlipidemia model rabbits,and to explore the possible mechanism.Methods:Forty New-Zea I a nd rabbits were ran domly divided into 5 groups using the ran dom nu mber table method,with 8 rats in each group.Rabbits in the blank group were fed routinely with normal diet;rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model.Rabbits in the blank and the model groups were not treated.After the model was prepared,rabbits in the non-transdermal absorption enhancer group received herbal cake-partitioned moxibustion without transdermal absorption enhancer;rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively.After 4 weeks of treatment,serum was collected for enzyme-linked immunosorbent assay(ELISA),and the liver tissues were isolated for imm uno histochemistry,qua ntitative polymerase chain reactio n(qPCR)and Western-blotting(WB)detecti on.Results:Serum ELISA results showed that leptin was significantly decreased in the model group compared with the blank group(P<0.05);compared with the model group,lepti n was significa ntly in creased in the non-tran sdermal absorpti on enhanee。the laurocapram and the borneol groups(all P<0.05);compared with the non-transdermal absorption enhancer group,leptin was significantly increased in the laurocapram group and the borneol group(both P<0.05);there was no significant differenee in leptin between the laurocapram and the borneol groups(P>0.05).The qPCR results of rabbit liver tissues showed that the mRNA expressions of leptin,Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STOT3)in the model group were significantly lower than those in the blank group(all P<0.05);compared with the model group,the mRNA expressions of leptin,leptin receptor(LR),JAK2 and S1AT3 in the non-transdermal absorptio n enhan cer,the laurocapram and the born eol groups were significantly in creased(all P<0.05);compared with the non-transdermal absorption enhancer group,the mRNA expressions of leptin,LR,JAK2 and S77VT3 in the laurocapram and the bor neol groups were sign ificantly in creased(all P<0.05);compared with the laurocapram group,the mRNA expressi ons of lepti n,LR,JAK2 and SW3 in the bor neol group were significa ntly in creased(P<0.05).The trend of immun ohistochemistry and WB detecti on results was basically con siste nt with the qPCR assay results.The immuno histochemistry and WB detection results of phosphorylated JAK2(phospho-JAK2)and phosphorylated S7AT3(phospho-STAT3)were basically consistent with those of JAK2 and S7AT3.Conclusion:The molecular expression of Leptin/JAK"S7AT3 pathway in the hyperlipidemia model rabbits was decreased.The molecular expression of Leptin/JAK0STCT3 pathway was significantly increased after the herbal cake-partitioned moxibustion.The application of laurocapram and borneol,as transdermal absorption enhancers,in the herbal cake-partitioned moxibustion could more obviously up-regulate the factors of the Leptin/JAK^SIAT3 lipid-regulating pathway than the herbal cake-partitioned moxibustion alone.

Effects of different transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids,HSL and HMG-CoA reductase in hyperlipidemia rabbits

Objective:To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids,hormone-sensitive lipase(HSL)and hydroxymethylglutaryl CoA(HMG-CoA)reductase in hyperlipidemia rabbits.Methods:Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method,with 8 rats in each group.Rabbits in the blank group were fed routinely with a normal diet;rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model.Rabbits in the blank and the model groups were not given any intervention.After the model was prepared successfully,rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers;rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively.After 4 weeks of treatment,the serum was isolated and enzyme-linked immunosorbent assay(ELISA)was applied for the detection of HSL and HMG-CoA reductase.The liver tissues were isolated,and total cholesterol(TC)and triglycerides(TG)were measured by enzymatic methods.One-step method was applied for high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)detection,and transmission turbidimetry was for apolipoprotein A1(Apo-A1)and apolipoprotein B(Apo-B)detection.Results:The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group(both P<0.05);all drug penetrations in the borneol group were significantly higher than those in the laurocapram group(both P<0.05),except for tanshinoneⅡA.Compared with the non-transdermal penetration enhancer group,the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups(both P<0.05);between groups,the HSL in the borneol group was significantly higher than that in the laurocapram group(P<0.05).Compared with the blank group,the levels of LDL-C,TG,TC and Apo-B in rabbit liver were significantly increased in the model group(P<0.05);compared with the model group,the levels of LDL-C,TG,TC and Apo-B in the non-transdermal penetration enhancer,the laurocapram,and the borneol groups were significantly decreased(all P<0.05);between groups,the TG and TC in the laurocapram group and the LDL-C,TG,TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group(all P<0.05),and the TG,LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group(all P<0.05).Compared with the blank group,the HDL-C and Apo-A1 were significantly decreased in the model group(both P<0.05),while compared with the model group,the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer,the laurocapram,and the borneol groups(all P<0.05).Between groups,the Apo-A1 in the laurocapram group,the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group(all P<0.05).Conclusion:The application of laurocapram and borneol,as transdermal penetration enhancers,in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake,increase the levels of HDL-C and Apo-A1,improve the metabolism of HSL and HMG-CoA reductase,and also simultaneously reduce the levels of TC,TG,LDL-C and Apo-B in the liver.The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.

Catharmus tinctorius volatile oil promote the migration of mesenchymal stem cells via ROCK2/Myosin light chain signaling

MSC transplantation has been explored as a new clinical approach to stem cell-based therapies for bone diseases in regenerative medicine due to their osteogenic capability. However, only a small population of implanted MSC could successfully reach the injured areas. Therefore, enhancing MSC migration could be a beneficial strategy to improve the therapeutic potential of cell transplantation. Catharmus tinctorius volatile oil(CTVO) was found to facilitate MSC migration. Further exploration of the underlying molecular mechanism participating in the pro-migratory ability may provide a novel strategy to improve MSC transplantation efficacy. This study indicated that CTVO promotes MSC migration through enhancing ROCK2 mRNA and protein expressions. MSC migration induced by CTVO was blunted by ROCK2 inhibitor, which also decreased myosin light chain(MLC) phosphorylation.Meanwhile, the si RNA for ROCK2 inhibited the effect of CTVO on MSC migration ability and attenuated MLC phosphorylation,suggesting that CTVO may promote BMSC migration via the ROCK2/MLC signaling. Taken together, this study indicates that C.tinctorius volatile oil could enhance MSC migration via ROCK2/MLC signaling in vitro. C. tinctorius volatile oil-targeted therapy could be a beneficial strategy to improve the therapeutic potential of cell transplantation for bone diseases in regenerative medicine.

Efficacy and Mechanism of Buxue Yimu Pillson Gynecological Anemia:A Combination of Clinical and Network Pharmacology Study

Objective:Tocompare the clinical efficacyand safety of oral administration of BuxueYimuPills(BYP),ferrous sulfate(FS),and the combination of BYP and FS on gynecological anemia,and investigate the mechanisms using network pharmacology.Methods:A randomized,controlled,multi-center clinical trial was conducted.Totally 150 patients with hemoglobin of 70-110 g/L due to gynecological conditions were recruited and randomized(using the block randomization method)into Buxue Yimu Pills group(24 g/d),oral iron group(FS Tablets,0.9 g/d),and combined treatment group(BYP,24g/d plus FS Tablets,0.9 g/d),50 patients in each group.At the enrollment and 4-week treatment,complete blood count,serum iron indexes were evaluated.Adverse events,liver and renal functions,as well as blood coagulation were observed.Network pharmacology was conducted to identify the active ingredients and explore the potential mechanisms of BYP.Results:Ten(20%)and 7(14%)participants discontinued the therapy due to gastrointestinal symptoms in oral iron and combination treatment groups.All 3 groups showed elevated hemoglobin.The patients in the iron group exhibited typically elevated in serum iron and ferritin and decreased in total iron-binding capacity.No change in iron indexes was observed in BYP group.The patients in the combination treatment group neither showed significant changes in serum ferritin nortotal iron-binding capacity.No significant adverse reactions were observed in the BYP group.The network pharmacology identified 27 bioactive compounds and 145 targets of BYP on gynecological anemia.Biological processes and pathways including regulation of inflammation,hormone,angiogenesis and hemostasis,responsetodecreased oxygen levels,effects on myeloma cell,and responseto metal ions were identified.Conclusion:BYP contributes to the practical improvement on gynecological anemia potentially through multi-target mechanisms and optimized iron re-distribution.

内关、公孙对功能性消化不良大鼠下丘脑-垂体-肾上腺轴的调节作用

目的:探讨内关、公孙对功能性消化不良(FD)模型大鼠下丘脑-垂体-肾上腺(HPA)轴的作用及可能机制,为八脉交会穴的临床应用提供理论依据.方法:将40只无特定病原体级Sprague-Dawley大鼠采用随机数字表法分为空白组、模型组、电针组和西药组,每组10只.空白组不造模,不干预.其他三组采用复合病因造模法制作FD伴情绪障碍模型.模型成功后,模型组不干预;西药组灌服黛力新合莫沙必利;电针组行电针干预,穴取同侧内关、公孙.治疗21 d.分别于实验前及治疗前后检测糖水消耗率以评定情绪状态;治疗后检测胃排空率评定胃肠动力;应用酶联免疫吸附法检测下丘脑促肾上腺皮质激素释放激素(CRH)、垂体促肾上腺皮质激素(ACTH)及肾上腺皮质酮(CORT)的表达水平.结果:与空白组相比较,模型组大鼠糖水消耗率及胃排空率均下降(P<0.01);下丘脑CRH、垂体ACTH及肾上腺CORT表达水平均上升(P<0.01).与模型组相比较,电针组和西药组大鼠糖水消耗率及胃排空率均明显提升(P<0.01);下丘脑CRH、垂体ACTH及肾上腺CORT表达水平明显下降(P<0.01).电针组与西药组各项差异均无统计学意义(P>0.05).结论:八脉交会穴之内关、公孙能改善FD大鼠的情绪及胃肠动力;其作用机制可能与降低下丘脑CRH、垂体ACTH和肾上腺CORT表达水平,纠正HPA轴功能亢进有关.