Latest Issue
      2020 Year 26 Vol. 9 Issue

        Hot Topic

      • Usman Ali,Evhy Apryani,Muhammad Zaeem Ahsan,Rana Muhammad Shoaib,Khalil Ali Ahmad,Yong-xiang WANG
        2020, 26(9): 643-647. DOI: 10.1007/s11655-019-3175-7
        Abstract：Opioid drugs are the first line of defense in severe pain but the adverse effects associated with opioids are considered as a serious issue worldwide. Acupuncture/electroacupuncture is a type of Chinese medicine therapy which is an effective analgesic therapy, well documented in animals and human studies. Electroacupuncture stimulation could release endogenous opioid peptides causing analgesia in a variety of pain models. It can be used as an alternative therapy to control the opioid crisis.  
        Keywords：analgesia;Chinese medicine;electroacupuncture;acupuncture;opioid crisis   
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        Published：2021-08-23

        Original Article

      • Jia-bo WANG,Zhong-xia WANG,Jing JING,Peng ZHAO,Jing-hui DONG,Yong-feng ZHOU,Guang YANG,Ming NIU,Xu ZHAO,Tian-jun JIANG,Jing-feng BI,Zhe XU,Ping ZHANG,Dan WU,Zhao-fang BAI,Yu-ming GUO,Si-miao YU,Yong-qiang SUN,Zi-teng ZHANG,Xiao-yan ZHAN,Peng-yan LI,Jin-biao DING,Peng-fei ZHAO,Xue-ai SONG,Jian-yuan TANG,Dong-chu HE,Zhu CHEN,En-qiang QIN,Rui-lin WANG,Xiao-he XIAO
        2020, 26(9): 648-655. DOI: 10.1007/s11655-020-3426-7
        Abstract：Objectives:To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients.Methods:A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 μg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed.Results:An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048).Conclusions:Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT 04251871 at www.clinicaltrials.gov)  
        Keywords：Covid-19;SARS-CoV-2;acute respiratory distress syndrome;Chinese medicine   
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        Published：2021-08-23
      • Yang OU,Sheng-jia SUN,Hai-ming SHI,Jian-feng LUO,Xin-ping LUO,Yun-zhi SHEN,Yu-fei CHEN,Wei-hu FAN,Hong-ying LIU,Wei SHEN
        2020, 26(9): 656-662. DOI: 10.1007/s11655-020-2728-0
        Abstract：Objective:To evaluate the protective effects of salvianolate on percutaneous coronary intervention (PCI) related myocardial injury or myocardial infarction after elective PCI in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients.Methods:A total of 149 patients with NSTE-ACS who underwent elective PCI were enrolled. The patients were randomly allocated in a 1:1 ratio to the salvianolate group (74 cases) or the control group (75 cases). After exclusion criteria of coronary angiography, 60 patients with PCI therapy remained in the salvianolate group and 68 in the control group. The incidence and the severity of PCI related myocardial injury or myocardial infarction, in addition to major adverse cardiac events (MACEs) during 1 year follow-up after PCI were studied between the two groups. Multivariate logistic regression analysis was used to determine the independent factors for PCI related myocardial injury or myocardial infarction after elective PCI.Results:Compared with the control group, salvianolate treatment reduced the incidence of PCI related severe myocardial injury or myocardial infarction (11.7% vs. 26.5%, P=0.035). The rate of MACEs or all-cause death within 1 month or 1 year after the procedure was not significantly different between the two groups.Conclusions:Periprocedural treatment with salvianolate reduces the incidence of PCI related severe myocardial injury or myocardial infarction, although it does not influence clinical prognosis. [Chinese clinical trial registry: ChiCTR1800016992]  
        Keywords：myocardial infarction;acute coronary syndrome;percutaneous coronary intervention;Salvianolate   
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        Published：2021-08-23
      • Tian-zi WEI,Hao WANG,Xue-qing WU,Yi LU,Sheng-hui GUAN,Feng-quan DONG,Chen-le DONG,Gu-li ZHU,Yu-zhou BAO,Jian ZHANG,Guan-yu WANG,Hai-ying LI
        2020, 26(9): 663-669. DOI: 10.1007/s11655-020-3427-6
        Abstract：Objective:To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening.Methods:The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper.Results:It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (莲花清瘟), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score.Conclusions:A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.  
        Keywords：Covid-19;SARS-CoV-2;drug repurposing;virtual screening;Chinese medicine   
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        Published：2021-08-23
      • Ki Sun Kwon,Hyun Lim,Yong Soo Kwon,Myong Jo Kim,Ji Hye Yoo,Nam Ho Yoo,Hyun Pyo Kim
        2020, 26(9): 670-676. DOI: 10.1007/s11655-020-3188-2
        Abstract：Objective:To study the anti-inflammatory action and cellular mechanism of Oplopanax elatus.Methods:A hot water extract of OE (WOE) was prepared and a major constituent, syringin, was successfully isolated. Its content in WOE was found to be 214.0 μg/g dried plant (w/w). Their anti-inflammatory activities were examined using RAW 264.7 macrophages and a mouse model of croton oil-induced ear edema.Results:In lipopolysaccharide (LPS)-treated RAW 264.7 cells, a mouse macrophage cell line, WOE was found to significantly and strongly inhibit cyclooxygenase-2 (COX-2)-induced prostaglandin E2 (PGE2) production [half maximal inhibitory concentration (IC50)=135.2 μg/mL] and inducible nitric oxide synthase (iNOS)-induced NO production (IC50=242.9 μg/mL). In the same condition, WOE was revealed to inhibit NO production by downregulating iNOS expression, mainly by interrupting mitogen activated protein kinases (MAPKs)/activator protein-1 (AP-1) pathway. The activation of all three major MAPKs, p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was inhibited by WOE (50–300 μg/mL). On the other hand, WOE reduced PGE2 production by inhibiting COX-2 enzyme activity, but did not affect COX-2 expression levels. In addition, WOE inhibited the production of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. In croton oil-induced ear edema in mice, oral administration of WOE (50–300 mg/kg) dose-dependently inhibited edematic inflammation.Conclusion:Water extract of OE exhibited multiple anti-inflammatory action mechanisms and may have potential for treating inflammatory disorders.  
        Keywords：Oplopanax elatus;Chinese medicine;stem;syringin;anti-inflammation;RAW 264.7   
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        Published：2021-08-23
      • Hyunjhung Jhun,Suji Baek,Jinwoo Kim,Kang-Pa Lee,Hun-Young Park,Won-Hwan Park,Kiwon Lim,Jisu Kim
        2020, 26(9): 677-682. DOI: 10.1007/s11655-019-3171-y
        Abstract：Objective:To investigate the effects of Korean Magnolia obovata crude extract (KME) on plateletderived growth factor (PDGF)-BB-induced proliferation and migration of vascular smooth muscle cells (VSMCs).Methods:KME composition was analyzed by high-performance liquid chromatography (HPLC). VSMCs were isolated from the aorta of a Sprague-Dawley rat, incubated in serum free-Dulbecco's modified Eagle's medium in the presence or absence of KME (10, 30, 100, and 300 μg/mL), then further treated with PDGF-BB (10 ng/mL). VSMC proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and VSMC migration was determined using the Boyden chamber and scratch wound healing assays. Western blot analysis was used to detect phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (p-ERK1/2), protein kinase B (p-Akt), and stress-activated protein kinase/c-Jun NH2-terminal kinase (p-SAPK/JNK). The antimigration and proliferation effects of KME were tested using aortic sprout outgrowth.Results:The HPLC analysis identified honokiol (0.45 mg/g) and magnolol (0.34 mg/g) as the major components of KME. KME (30, 100, and 300 μg/mL) significantly decreased the proliferation and migration of PDGF-BB-stimulated (10 ng/mL) VSMCs and the PDGF-BB-induced phosphorylation of EKR1/2, Akt, and SAPK/JNK (P<0.05). Furthermore, PDGF-BBinduced VSMCs treated with 300 μg/mL of KME showed reduction in aortic sprout outgrowth.Conclusion:KME could inhibit abnormal proliferation and migration of VSMCs by down-regulating the phosphorylation of EKR1/2 and Akt. Thus, KME might be a functional food for preventing vascular disorders.  
        Keywords：extracellular signal-regulated protein kinases 1 and 2;Akt;platelet-derived growth factor-BB;smooth muscle cell;functional food   
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        Published：2021-08-23
      • Zahra Ehtemami,Hamed Shafaroodi,Jinous Asgarpanah
        2020, 26(9): 683-687. DOI: 10.1007/s11655-020-3424-9
        Abstract：Objective:To evaluate the effects of Zhumeria majdae essential oil (ZMEO) on morphine dependence and tolerance in mice.Methods:ZMEO (10, 20, and 40 mg/kg) and clonidine (0.1 mg/kg) as the positive control were injected intraperitoneally (i.p.). The effect of ZMEO and clonidine on the dependence were evaluated by counting the number of jumps induced by naloxone (5 mg/kg) while the tolerance was evaluated by the tail-flick test.Results:ZMEO at the dose of 10 mg/kg during the development period led to a significant inhibition of morphine tolerance (P<0.01), while it led to reduced morphine dependence with the doses of 20 and 40 mg/kg. ZMEO at two dose levels of 20 and 40 mg/kg indicated significant antinociceptive activity (P<0.01), and significantly reduced the withdrawal signs (number of jumps) of mice (P<0.01).Conclusions:ZMEO had significant effects on morphine tolerance and dependence. The linalool rich essential oil of Z. majdae plays a major role in the reduction of tolerance and dependence induced by morphine.  
        Keywords：Zhumeria majdae;morphine;dependence;tolerance   
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        Published：2021-08-23
      • Suzy Jo,Junghyun Ryu,Hanna Kim,Miyoung Kim,Mi Heon Ryu,Hyungwoo Kim,Su-In Cho
        2020, 26(9): 688-693. DOI: 10.1007/s11655-015-2148-8
        Abstract：Objective:To investigate the anti-inflammatory effects of Sanguisorbae Radix on contact dermatitis (CD).Methods:Mice were sensitized by painting 30 μL of 1-fluoro-2,4-dinitrofluorobenzene (DNFB) onto each ear for 3 days. Four days later, mice were challenged by painting with 50 μL of DNFB onto the shaved dorsum every 2 days. Sanguisorbae Radix methanol extract (MESR) was applied onto the shaved dorsum every 2 days. The effects of MESR on skin thickness, skin weights, histopathological changes, skin lesions and cytokine production in DNFB-induced CD mice were investigated, as well as its effects on body weights and spleen/body weight ratio.Results:Topical application of MESR effectively inhibited enlargement of skin thickness and weight (P<0.05). MESR treatment also inhibited hyperplasia, spongiosis and immune cell infiltration induced by DNFB in inflamed tissues and improved lesions on dorsum skin in CD mice. Moreover, treatment with MESR suppressed the increase in the levels of tumor necrosis factor α (TNF-α, P<0.01) and interferon γ (IFN-γ, P<0.05), respectively. Finally, MESR had no effect on body weight gain or spleen/body weight ratio.Conclusion:These data suggest that MESR acts as an anti-inflammatory agent that decreases the production of TNF-α and IFN-γ, resulting in reductions of skin lesions and histopathological changes in inflamed skin tissues.  
        Keywords：Sanguisorba officinalis;skin diseases;herbal;Chinese materia medica   
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        Published：2021-08-23

        Acupuncture Research

      • Jing-ke GUO,Jin-sen XU,Tian-bao CHEN,Ming-ming XU,Shu-tao LIU,Chao-xin ZHANG,Li-jing KE,Jian-wu ZHOU,Qiang WANG,Ping-fan RAO
        2020, 26(9): 694-700. DOI: 10.1007/s11655-019-3173-9
        Abstract：Objectives:To investigate the effect on essential hypertension of the topical application of TAT-Cu, Zn-superoxide dismutase (TAT-SOD) at left acupoint Zusanli (ST 36), and to observe whether the change of electrical potential difference (EPD) can be related to the change of blood pressure.Methods:Sixteen patients with essential hypertension and 16 healthy subjects were included in the study. EPD between the left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) was firstly screened out for the EPD detection. An intracellular superoxide quenching enzyme, TAT-SOD, was topically applied to the acupoint ST 36 within an area of 1 cm2 once a day, and the influence on EPD was investigated. The dosage applied to TAT-SOD group (n=8) was 0.2 mL of 3000 U/mL TAT-SOD cream prepared by adding purified TAT-SOD to a vehicle cream, while placebo group (n=8) used the vehicle cream instead. The left acupoints of Yanglingquan (GB 34) and Qiuxu (GB 40) were selected for EPD measurement after comparing EPD readings between 5 acupoints on each of all 12 meridians.Results:EPDs between the left acupoints of GB 34 and GB 40 for 16 patients of essential hypertension and 16 healthy subjects were 44.9±6.4 and 5.6±0.9 mV, respectively. Daily application of TAT-SOD for 15 days at ST 36 of essential hypertension patients significantly decreased systolic blood pressure (SBP) and diastolic blood pressure (DBP) of 179.6 and 81.5 mm Hg to 153.1 and 74.1 mm Hg, respectively. Responding to the change in blood pressure, EPD between the left acupoints of GB 34 and GB 40 also declined from 44.4 to 22.8 mV with the same trend. No change was observed with SBP, DBP and EPD between the left acupoints of GB 34 and GB 40 with the daily application of the placebo cream.Conclusion:Enzymatic scavenging of the intracellular superoxide at ST 36 proved to be effective in decreasing SBP and DBP. The results reconfirm the involvement of superoxide anions and its transportation along the meridians, and demonstrate that EPD between acupoints may be an indicator to reflect its functioning status. Moreover, preliminary results suggest a close correlation between EPD and blood pressure readings, implying a possibility of using EPD as a sensitive parameter for blood pressure and to monitor the effect of antihypertensive treatment.  
        Keywords：TAT-SOD;reactive oxygen species;electrical potential;essential hypertension;acupoints   
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        Published：2021-08-23
      • Min LI,Ke WANG,Wen-ting SU,Jun JIA,Xiao-min WANG
        2020, 26(9): 701-708. DOI: 10.1007/s11655-017-2975-x
        Abstract：Objective:To explore the possible underlying mechanism by investigating the effect of electroacupuncture (EA) treatment on the primary motor cortex and striatum in a unilateral 6-hydroxydopamine (6-OHDA) induced rat Parkinson's disease (PD) model.Methods:Male Sprague-Dawley rats were randomly divided into sham group (n=16), model group (n=14), and EA group (n=14). EA stimulation at Dazhui (GV 14) and Baihui (GV20) was applied to PD rats in the EA group for 4 weeks. Behavioral tests were conducted to evaluate the effectiveness of EA treatment. Metabolites were detected by 7.0 T proton nuclear magnetic resonance.Results:Following 4 weeks of EA treatment in PD model rats, the abnormal behavioral impairment induced by 6-OHDA was alleviated. In monitoring changes in metabolic activity, ratios of myoinositol/creatine (Cr) and N-acetyl aspartate (NAA)/Cr in the primary motor cortex were significantly lower at the injected side than the non-injected side in PD rats (P=0.024 and 0.020). The ratios of glutamate + glutamine (Glx)/Cr and NAA/Cr in the striatum were higher and lower, respectively, at the injected side than the non-injected side (P=0.046 and 0.008). EA treatment restored the balance of metabolic activity in the primary motor cortex and striatum. In addition, the taurine/Cr ratio and Glx/Cr ratio were elevated in the striatum of PD model rats compared to sham-lesioned rats (P=0.026 and 0.000). EA treatment alleviated the excessive glutamatergic transmission by down-regulating the striatal Glx/Cr ratio (P=0.001). The Glx/Cr ratio was negatively correlated with floor plane spontaneous locomotion in PD rats (P=0.027 and P=0.0007).Conclusions:EA treatment is able to normalize the metabolic balance in the primary motor cortex and striatum of PD rats, which may contribute to its therapeutic effect on motor deficits. The striatal Glx/Cr ratio may serve as a potential indicator of PD and a therapeutic target of EA treatment.  
        Keywords：electroacupuncture;magnetic resonance spectroscopy;motor cortex;striatum;Parkinson's disease   
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        Published：2021-08-23

        Evidence-Based Integrative Medicine

      • Chan-Young Kwon,Sang-Hoon Yoon,Sun-Yong Chung,Jong Woo Kim
        2020, 26(9): 713-720. DOI: 10.1007/s11655-020-3179-3
        Abstract：Objective:To investigate the clinical efficacy and safety of miniscalpel-needle (MSN) treatment for tension-type headache (TTH).Method:Seven medical databases were searched to identify randomized controlled trials (RCTs) evaluating the effect and safety of MSN treatment. All articles published up to November 15, 2018 were retrieved. A meta-analysis was conducted for the included studies, and the risk of bias was assessed. Primary outcomes were visual analogue scale (VAS) or numeric rating scale (NRS) score. Secondary outcomes were clinical effective rates including total effective rate (TER), markedly effective rate (MER), and totally cured rate (TCR) determined by improvement in clinical symptoms or VAS scores, the frequency of adverse events (AEs) that occurred during the study, and participant quality of life (QOL).Results:Seven RCTs involving 724 participants were included. MSN treatment showed significantly higher MER and TCR [relative risk (RR) 1.27, 95% confidence interval (CI) 1.01 to 1.61; RR 1.31, 95% CI 1.09 to 1.57, respectively], but not TER (RR 1.03, 95% CI 0.96 to 1.10) compared to acupuncture. MSN treatment plus conventional treatment showed significant lower VAS and higher TER, MER, and TCR (mean difference –3.54, 95% CI –3.80 to –3.28; RR 1.14, 95% CI 1.06 to 1.23; RR 2.31, 95% CI 1.50 to 3.58; RR 3.01, 95% CI 2.25 to 4.02, respectively) compared to conventional treatment.Conclusions:According to current evidence, MSN treatment as a monotherapy or as an adjunctive treatment to other existing treatments might have benefits on treating TTH. However, since the number and the sample size of studies included were both small and the methodological quality was poor, the findings of this review should be interpreted with great caution, and our confidence in the results is low. A high quality RCT using objective outcomes should be performed on this topic.  
        Keywords：acupuncture;acupotomy;tension-type headache;systematic review;meta-analysis   
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        Published：2021-08-23
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