Chinese Journal of Integrative Medicine

Zhan, Jia-wen; Li, Kai-ming; Zhu, Li-guo; Wang, Shang-quan; Feng, Min-shan; Wei, Xu; Yu, Jie; Tang, Bin; Yin, Xun-lu; Han, Tao; Zhang, Ping; Li, Ling-hui; Chen, Ming; Shao, Chen-chen

doi: 10.1007/s11655-022-3505-4pmid: 35840851

ObjectiveTo assess the efficacy and safety of Bushen Huoxue Formula (BSHXF) for the treatment of discogenic low-back pain (DLBP).MethodsThis was a parallel, double-blind, randomized, clinical trial performed between May 2019 and June 2020. Seventy patients were assigned by computerized random number table to the treatment group (lumbar traction and BSHXF, 35 cases) or the control group (lumbar traction and placebo, 35 cases). The patients received intervention for 3 weeks. Assessment was conducted before treatment and at week 1, 2, 3 during treatment. Primary outcome was the self-reported score of Oswestry Disability Index (ODI). Secondary outcomes included Visual Analog Scale (VAS), clinical efficacy rate by minimal clinically important difference (MCID) as well as lumbar tenderness, muscle tone and lumbar spine mobility. Adverse reactions were recorded. Follow-up was performed at 1 and 3 months after the end of treatment.ResultsIn the treatment group, ODI score was significantly decreased compared with baseline (P<0.05) and the control group at 2- and 3- week treatment. Similarly, VAS score decreased compared with the baseline (P<0.05) and was lower than that in the control group at 2- and 3- week treatment (P<0.05). The clinical efficacy rate of the treatment group was higher than that of the control group after treatment [32.35% (11/34) vs. 3.13% (1/32), P<0.05). Moreover, the tenderness, and muscle tone, as well as the back extension and left flexion in lumbar spine mobility in the treatment group at 3-week treatment were significantly improved compared with the control group (P<0.05). Follow-up showed that at 1-month after treatment, the treatment group had better outcomes than the control group with regard to a total score of ODI and VAS scores, as well as clinical efficacy rate (all P<0.05). Moreover, VAS score was still significantly lower than the control group at 3-month follow-up (P<0.05). No adverse reactions were reported during the study.ConclusionBSXHF combined with lumbar traction can significantly improve the clinical symptoms including pain intensity, functionality, muscle tone, and lumbar spine mobility in DLBP patients. (Registration No. ChiCTR1900027777).

Zhang, Tong; Xu, Yun; Sun, Ling-yun; He, Bin; Hao, Jie; Zhang, Da; Yang, Yu-fei

doi: 10.1007/s11655-021-3281-1pmid: 34755287

ObjectiveTo verify the efficacy of Quxie Capsule in patients with metastatic colorectal cancer (mCRC).MethodsIt was a block randomized, double-blind, placebo-controlled trial. Sixty patients with mCRC were randomized into 2 groups at a 1:1 ratio. The patients in the treatment group received conventional therapy including chemotherapy, radiotherapy, targeted therapy and supportive care, and Chinese herbal medicine combined with Quxie Capsule (each capsule of 0.4 g was orally administered at 50 mg/kg, twice daily, day 1–20, in a 30-day course) for 3 months. The patients in the control group received conventional therapy and Chinese herbal medicine combined with placebo for 3 months. Main outcome measures were overall survival (OS) and progression-free survival (PFS). Subgroup analysis was performed according to therapy lines, right or left-sided colon, targeted therapy and RAS gene status to determine the differences in PFS and OS between the two groups. Patients were followed up every 3 months until December 31st, 2018.ResultsMedian follow-up time was 19.4 months. The median OS was 23.9 months in the treatment group [95% confidence interval (CI) 15.9–28.5] vs. 14.3 months in the control group (95% CI 11.3–21.4, P<;0.05). Hazard ratio (95% CI) was 0.55 (0.31–0.95, P=0.040). There were no significant differences between the two groups in PFS (P>0.05). In the subgroups of ⩾second-line therapy, non-targeted therapy, RAS gene wild type and left-sided colon, the treatment group showed a significant survival benefit compared with the control group (P<;0.05 or P<;0.01), respectively.ConclusionQuxie Capsule can reduce the risk of death and prolong the OS of patients with mCRC. (Registration No. ChiCTR-IOR-16009733)

Zhang, Yan-nan; Guo, Yi-qiong; Fan, Yan-na; Tao, Xiu-juan; Gao, Qing-han; Yang, Jian-jun

doi: 10.1007/s11655-021-3309-6pmid: 34874519

ObjectiveTo explore the protective effect and underlying mechanism of Lycium barbarum polysaccharides (LBP) in a non-alcoholic fatty liver disease (NAFLD) cell model.MethodsNormal human hepatocyte LO2 cells were treated with 1 mmol/L free fatty acids (FFA) mixture for 24 h to induce NAFLD cell model. Cells were divided into 5 groups, including control, model, low-, medium- and high dose LBP (30,100 and 300 µg/mL) groups. The monosaccharide components of LBP were analyzed with high performance liquid chromatography. Effects of LBP on cell viability and intracellular lipid accumulation were assessed by cell counting Kit-8 assay and oil red O staining, respectively. Triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), adenosine triphosphate (ATP) and oxidative stress indicators were evaluated. Energy balance and mitochondrial biogenesis related mRNA and proteins were determined by quantitative real-time polymerase chain reaction and Western blot, respectively.ResultsHeteropolysaccharides with mannose and glucose are the main components of LBP. LBP treatment significantly decreased intracellular lipid accumulation as well as TG, ALT, AST and malondialdehyde levels (P<0.05 or P<0.01), increased the levels of superoxide dismutase, phospholipid hydroperoxide glutathione peroxidase, catalase, and ATP in NAFLD cell model (P<0.05). Meanwhile, the expression of uncoupling protein 2 was down-regulated and peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor 1/mitochondrial transcription factor A pathway was up-regulated (P<0.05).ConclusionLBP promotes mitochondrial biogenesis and improves energy balance in NAFLD cell model.

Mei, Sheng-lan; Xia, Zhong-yuan; Qiu, Zhen; Jia, Yi-fan; Zhou, Jin-jian; Zhou, Bin

doi: 10.1007/s11655-022-3620-xpmid: 35997859

ObjectiveTo examine the effect of Shenmai Injection (SMJ) on ferroptosis during myocardial ischemia reperfusion (I/R) injury in rats and the underlying mechanism.MethodsA total of 120 SPF-grade adult male SD rats, weighing 220–250 g were randomly divided into different groups according to a random number table. Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion. SMJ was injected intraperitoneally at the onset of 120 min of reperfusion, and erastin (an agonist of ferroptosis), ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) and ML385 (an inhibitor of nuclear factor erythroid-2 related factor 2 (Nrf2)) were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments. Cardiac function before ischemia, after ischemia and after reperfusion was analysed. Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed, and the myocardial infarction area was measured. Additionally, the concentration of Fe2+ in heart tissues and the levels of creatine kinase-MB (CK-MB), troponin I (cTnl), malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were measured using assay kits, and the expressions of Nrf2, glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member 4 (ACSL4) were examined by Western blot.ResultsCompared with the sham group, I/R significantly injured heart tissues, as evidenced by the disordered, ruptured and oedematous myocardial fibres; the increases in infarct size, serum CK-MB, cTnI and MDA levels, and myocardial Fe2+ concentrations; and the decreases in SOD activity (P<0.05). These results were accompanied by ultrastructural alterations to the mitochondria, increased expression of ACSL4 and inhibited the activation of Nrf2/GPX4 signalling (P<0.05). Compared with I/R group, pretreatment with 9 mL/kg SMJ and 2 mg/kg Fer-1 significantly reduced myocardial I/R injury, Fe2+ concentrations and ACSL4 expression and attenuated mitochondrial impairment, while 14 mg/kg erastin exacerbated myocardial I/R injury (P<0.05). In addition, cardioprotection provided by 9 mL/kg SMJ was completely reversed by ML385, as evidenced by the increased myocardial infarct size, CK-MB, cTnI, MDA and Fe2+ concentrations, and the decreased SOD activity (P<0.05).ConclusionsFerroptosis is involved in myocardial I/R injury. Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis, thereby providing a strategy for the prevention and treatment of ischemic heart diseases.

Zheng, Yang; Wang, Lei; Wang, Jia-hui; Liu, Lu-lu; Zhao, Tie-jian

doi: 10.1007/s11655-021-3310-0pmid: 34319504

ObjectiveTo investigate the effect of curcumol on NOD-like receptor thermoprotein domain 3 (NLRP3) inflammasomes, and analyze the mechanism underlying curcumol against liver fibrosis.MethodsThirty Kunming mice were divided into a control group, a model group and a curcumol group according to a random number table, 10 mice in each group. Mice were intraperitoneally injected with 40% carbon tetrachloride (CCl4:peanut oil, 2:3 preparation) at 5 mL/kg for 6 weeks, twice a week, for developing a liver fibrosis model. The mice in the control group were given the same amount of peanut oil twice a week for 6 weeks. The mice in the curcumol group were given curcumol (30 mL/kg) intragastrically, and the mice in the model and control groups were given the same amount of normal saline once a day for 6 weeks. Changes in liver structure were observed by hematoxylin and eosin (HE) and Masson staining. Liver function, liver fiber indices, and the expression of interleukin (IL)-10 and tumor necrosis factor-α (TNF-α) levels were determined by automatic biochemical analyzer and enzyme linked immunosorbent assay kit. Immunoblotting and reverse transcription-quantitative PCR (RT-qPCR) were performed to detect the expression of NLRP3 inflammasome-related molecules, TGF-β and collagen.ResultsHE and Masson staining results showed that the hepatocytes of the model group were arranged irregularly with pseudo-lobular structure and a large amount of collagen deposition. The mice in the curcumol group had a significant decrease in liver function and liver fibers indices compared with the model group (P<0.05); RT-qPCR and Western blotting results reveal that, in the curcumol group, the mRNA and protein expression levels of NLRP3, IL-1 β, Caspase 1 and gasdermin D decreased significantly compared with the model group (P<0.05); immunohistochemical results showed that in the curcumol group, the protein expression levels of NLRP3 and IL-1 β decreased significantly compared with the model group (P<0.05).ConclusionA potential anti-liver fibrosis mechanism of curcumol may be associated with the inhibition of NLRP3 inflammasomes and decreasing the downstream inflammatory response.

Gui, Meng-xuan; Huang, Bin; Peng, Jun; Chen, Xi; Muthu, Ragunath; Gao, Ying; Wang, Rui-guo; Lin, Jiu-mao

doi: 10.1007/s11655-021-3282-0pmid: 33420580

ObjectiveTo evaluate the protective function of Babao Dan (BBD) on 5-flurouracil (5-FU)-induced intestinal mucositis (IM) and uncover the underlying mechanism.MethodsA total of 18 male mice were randomly divided into 3 groups by a random number table, including control, 5-FU and 5-FU combined BBD groups, 6 mice in each group. A single intraperitoneal injection of 5-FU (150 mg/kg) was performed in 5-FU and 5-FU combined BBD groups on day 0. Mice in 5-FU combined BBD group were gavaged with BBD (250 mg/kg) daily from day 1 to 6. Mice in the control group were gavaged with saline solution for 6 days. The body weight and diarrhea index of mice were recorded daily. On the 7th day, the blood from the heart of mice was collected to analyze the proportional changes of immunological cells, and the mice were subsequently euthanized by mild anesthesia with 2% pentobarbital sodium. Colorectal lengths and villus heights were measured. Intestinal-cellular apoptosis and proliferation were evaluated by Tunel assay and immunohistochemical staining of proliferating cell nuclear antigen, respectively. Immunohistochemistry and Western blot were performed to investigate the expressions of components in Wnt/β-catenin pathway (Wnt3, LRP5, β-catenin, c-Myc, LRG5 and CD44).ResultsBBD obviously alleviated 5-FU-induced body weight loss and diarrhea, and reversed the decrease in the number of white blood cells, including monocyte, granulocyte and lymphocyte, and platelet (P<0.01). The shortening of colon caused by 5-FU was also reversed by BBD (P<0.01). Moreover, BBD inhibited apoptosis and promoted proliferation in jejunum tissues so as to reduce the intestinal mucosal damage and improve the integrity of villus and crypts. Mechanically, the expression levels of Wnt/β -catenin mediators such as Wnt3, LRP5, β-catenin were upregulated by BBD, activating the transcription of c-Myc, LRG5 and CD44 (P<0.01).ConclusionsBBD attenuates the adverse effects induced by 5-FU via Wnt/β-catenin pathway, suggesting it may act as a potential agent against chemotherapy-induced intestinal mucositis.

Wang, Cui-fang; Cai, Xiao-rong; Chi, Yan-ni; Miao, Xiao-yao; Yang, Jian-yun; Xiao, Bing-kun; Huang, Rong-qing

doi: 10.1007/s11655-021-3277-xpmid: 33881717

ObjectiveTo compare the analgesic effect of Jin Ling Zi Powder (JLZ) and its two single herbs.MethodsThe hot plate method was used to induce pain. Totally 36 mice were randomly divided into 6 groups by a complete random design, including control, model, aspirin (ASP, 0.14 g/kg body weight), JLZ (14 g/kg body weight), Corydalis yanhusuo (YHS, 14 g/kg body weight), and Toosendan Fructus (TF, 14 g/kg body weight) groups, 6 mice in each group. The mice in the control and model groups were given the same volume of saline, daily for 2 consecutive weeks. At 30, 60, 90, and 120 min after the last administration, the pain threshold of mice in each group was measured, and the improvement rate of pain threshold was calculated. Serum endogenous metabolites were analyzed by gas chromatography-mass spectrometry (GC-MS).ResultsThere was no statistical difference in pain threshold among groups before administration (P>0.05). After 2 weeks of administration, compared with the model group, the pain threshold in JLZ, YHS, TF and ASP groups were increased to varying degrees (P<0.05). JLZ had the best analgesic effect and was superior to YHS and TF groups. A total of 14 potential biomarkers were screened in serum data analysis and potential biomarkers levels were all reversed to different degrees after the treatment with JLZ and its single herbs. These potential biomarkers were mainly related to glyoxylate and dicarboxylate metabolism, glycine, serine and threonine metabolism, valine, leucine and isoleucine biosynthesis, aminoacyl-tRNA biosynthesis and inositol phosphate metabolism.ConclusionsThe analgesic mechanism of JLZ and YHS was mainly due to the combination of glycine and its receptor, producing post-synaptic potential, reducing the excitability of neurons, and weakening the afferent effect of painful information.

Wang, Ling; Tao, Jin-hua; Chen, Yi-fan; Shen, Yu-meng; Jiang, Shu

doi: 10.1007/s11655-021-3299-4pmid: 34586559

ObjectiveTo elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics.MethodsThirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software.ResultsThe metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels.ConclusionsThe study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.

Zhao, Guo-zhen; Li, Bo; Wang, Ya-fan; Guo, Shi-qi; Du, Yuan; Ma, Qiu-xiao; Guo, Yu-hong; Liu, Qing-quan

doi: 10.1007/s11655-022-3524-9pmid: 35508864

ObjectiveTo perform a systematic review to assess the effectiveness and safety of Reduning Injection versus neuraminidase inhibitors in treatment of influenza.MethodsThe MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Chinese Bio-medical Literature and Retrieval System (Sinomed), China National Knowledge Infrastructure Database (CNKI), China Science and Technology Journal Database (VIP), Wanfang Data Knowledge Service Platform and ClinicalTrails.gov were systematically searched from inception dates to May 2021 for randomized controlled trials (RCTs) exploring Reduning Injection alone or in combination with neuraminidase inhibitors in patients with influenza. Statistical analysis was performed using RevMan 5.4 and Stata 15.1. The qualities of the involved studies were assessed by the risk of bias according to the Cochrane handbook. The evidence quality of each outcome was evaluated by GRADEpro GDT.ResultsTwelve trials with 1,460 patients were included. The included studies had a certain unclear or high risk of bias. Reduning Injection appeared to be more effective in shortening the fever clearance time (MD: −16.20 h, 95% CI: −19.40 to −12.99, 7 trials, 814 patients, I2=94%, very low certainty), fever alleviation time (MD: −4.09 h, 95% CI: −4.22 to −3.96, 3 trials, 366 patients, I2=0%, low certainty), cough alleviation time (MD: −21.34 h, 95% CI: −41.56 to −1.11, 2 trials, 228 patients, I2=89%, very low certainty), fatigue alleviation time (MD: −31.83 h, 95% CI: −36.88 to −26.77, 2 trials, 270 patients, I2=0%, low certainty), sore throat alleviation time (MD: −28.66 h, 95% CI: −32.23 to −25.10, 1 trial, 150 patients, low certainty), and improving the total effective rate (RR: 1.15, 95% CI: 1.06 to 1.25, 10 trials, 1,074 patients, I2=76%, very low certainty). Besides, Reduning Injection seemed generally safe.ConclusionsThis study provided low or very low evidence indicating Reduning Injection may be effective in the treatment of influenza and might be safe. Further rigorously designed studies are needed to confirm the effectiveness and safety of Reduning Injection and support it as a recommendation for influenza.

Feng, Wu-wen; Liu, Juan; Cheng, Hao; Peng, Cheng

doi: 10.1007/s11655-021-3305-xpmid: 34755290

Chinese medicines (CM) are gaining more attentions from all over the world. However, there are a large body of questions to be answered because of the chemical complexity of CM and intricate molecular reactions within human body. In recent years, gut microbiota and metabolomics have emerged as two cynosures in deciphering the mechanisms of how our body is functioning. Since gut microbiota and host is a closely interrelated system, paying attention only to gut microbiota or metabolites may omit the interplays among CM, gut microbiota, and hosts. To systemically study these interplays, a network understanding of CM components, gut microbiota, metabolites of gut microbiota, metabolites in human body is necessary. Although there are some obstacles impeding the application of this integrative approach, the potential areas for implementation of the integrative approach is vast. These areas include, but not limited to, elucidating the mechanisms of CM at system level, screening bioactive compounds in CM, and guiding quality control of CM.