The American Journal of Chinese Medicine

Chronic low back pain is one of the most common reasons that people seek medical treatment, and the consequent disability creates a great financial burden on individuals and society. The etiology of chronic low back pain is not clear, which means it is often refractory to treatment. Acupuncture has been reported to be effective in providing symptomatic relief of chronic low back pain. However, it is not known whether the effects of acupuncture are due to the needling itself or nonspecific effects arising from the manipulation. To determine the effectiveness of acupuncture therapy, a meta-analysis was performed to compare acupuncture with sham acupuncture and other treatments. Overall, 2678 patients were identified from thirteen randomized controlled trials. The meta-analysis was performed by a random model (Cohen's test), using the I-square test for heterogeneity and Begg's test to assess for publication bias. Clinical outcomes were evaluated by pain intensity, disability, spinal flexion, and quality of life. Compared with no treatment, acupuncture achieved better outcomes in terms of pain relief, disability recovery and better quality of life, but these effects were not observed when compared to sham acupuncture. Acupuncture achieved better outcomes when compared with other treatments. No publication bias was detected. Acupuncture is an effective treatment for chronic low back pain, but this effect is likely to be produced by the nonspecific effects of manipulation.

To identify a safe and effective Impaired Glucose Tolerance (IGT) intervention program using Traditional Chinese Medicine (TCM) supported by Standard Health Care Advice (SHCA) for the evidence-based TCM intervention in IGT and evidence-based prevention of type 2 diabetes. A total of 510 IGT patients were randomly assigned into either control or TCM intervention group (255 patients for each group). The control group received standard health care according to SHCA. The intervention group also received TCM intervention in addition to standard health care. The study was conducted over a three-year follow-up. At the end of three years follow-up, accumulative incidence and average annual incidence rate of diabetes in the control group was 43.86% and 14.62% respectively. Accumulative incidence and average annual incidence rate of diabetes in the TCM intervention group was 22.17% and 7.39% respectively. Compared with the control treatment, TCM intervention can reduce the relative risk of IGT patients progressing to type 2 diabetes by 49.45% and absolute risk by 21.69%. In the TCM intervention group, oral glucose tolerance test (OGTT), 2 h glucose, glycated hemoglobin, insulin resistance and body mass index were all significantly improved when compared to the control group. No significant side effect was observed during the follow-up in the TCM group. The SHCA-supported TCM intervention can reduce the conversion rate of IGT to diabetes and improve insulin resistance; therefore, it is a safe and effective IGT intervention strategy.

A prospective multicenter clinical trial was conducted to compare the beneficial effects of a Chinese herbal medicine formula Jiangzhuoqinggan (JZQG) and western antihypertension drug irbesartan. JZQG is mainly composed of rhubarb, coptis, cassia, and uncaria. A total of 240 patients with mild to moderate hypertension were enrolled in the trial. Patients were assigned into two groups after screening: JZQG group and the irbesartan group. After four weeks of treatment, we compared the changes in routine blood pressure, 24 h ambulatory blood pressure, and waist circumference. There was a significant reduction in systolic blood pressure and diastolic blood pressure in the JZQG group (both p < 0.01). There were no significant differences between the reduction of systolic and diastolic blood pressures in the two treatment groups. From the 24 h ambulatory blood pressure measurement, the JZQG group showed a greater reduction in both systolic and diastolic blood pressures (in both daytime and nighttime) than the irbesartan group. Furthermore, there was a significant difference in waist circumference in the JZQG group (1.51 cm reduction; P < 0.05) but not the irbesartan group (0.42 cm). Thus, the JZQG formula may have therapeutic value in patients with both hypertension and metabolic syndrome.

While exercise has been shown to reduce the negative effects of substance withdrawal symptoms, no research has investigated if Tai Chi, a traditional Chinese exercise, has similar effects. Here, we observed the physiological effects of Tai Chi on protracted abstinence syndrome (PAS) in female heroin addicts by comprehensively inspecting their immune system function, complete blood count, hepatic function and renal function. To determine the psychological effects, we used the Hamilton Rating Scale for Depression (HRSD) and the rating scale of heroin withdrawal symptoms. We recruited 70 heroin-addicted young women beginning to undergo withdrawal and randomly assigned them into two groups: one group received one-hour Tai Chi exercise every two days (Tai Chi group, n = 36) and the other group did not (control group, n = 34). Thirty-three patients finished this six-month trial. Numerous significant physiological differences were observed between all heroin-addicted subjects (n = 70) and age-matched healthy individuals (n = 18), suggesting a deleterious effect of drug addiction. There were improvements for certain physical parameters between the Tai Chi group (n = 17) and the control group (n = 16), although the differences were not statistically significant. We observed a small significant difference in psychological effects near the 60-day mark between the two groups. Taken together, our results suggest that Tai Chi might have a positive effect on PAS, which future studies can confirm by using an expanded sample size, longer trial time, and more sensitive and specific indicators of psychological and physiological health.

Curcumin, an agent traditionally utilized for its preventative action against tumorigenesis, oxidation, inflammation, apoptosis and hyperlipemia, has also been used in the treatment of Alzheimer's disease (AD). Recent advances in the study of AD have revealed astrocytes (AS) as being key factors in the early pathophysiological changes in AD. Glial fibrillary acidic protein (GFAP), a marker specific to AS, is markedly more manifest during morphological modifications and neural degeneration signature during the onset of AD. Several studies investigating the functionality of curcumin have shown that it not only inhibits amyloid sedimentation but also accelerates the disaggregation of amyloid plaque. Thus, we are interested in the relationship between curcumin and spatial memory in AD. In this study, we intend to investigate the effects of curcumin in amyloid-β (Aβ_1-40) induced AD rat models on both the behavioral and molecular levels, that is to say, on their spatial memory and on the expression of GFAP in their hippocampi. Our results were statistically significant, showing that the spatial memory of AD rats improved following curcumin treatment (p < 0.05), and that the expression of GFAP mRNA and the number of GFAP positive cells in the curcumin treated rats was decreased relative to the AD group rats (p < 0.05). Furthermore, the expression level of GFAP mRNA in hippocampal AS in the AD rats significantly increased when compared with that in the sham control (p < 0.05). Taken together, these results suggest that curcumin improves the spatial memory disorders (such disorders being symptomatic of AD) in Aβ_1-40-induced rats by down regulating GFAP expression and suppressing AS activity.

Mesangial cell proliferation is correlated with the progression of renal failure. The purpose of this study was to determine whether a water extract of Poria cocos Wolf (WPC), a well-known medicinal plant, regulates rat mesangial cell proliferation in the presence of high glucose (HG). HG significantly accelerated [³H]-thymidine incorporation, which was inhibited by WPC (1–50 μg/mL) in a dose-dependent manner. Cell migration and fibronectin mRNA expression data also supported the anti-proliferative effect of WPC. Western blot analysis revealed that pretreatment with WPC decreased the expression of cyclins and cyclin-dependent kinases (CDKs) and promoted the expression of p21^waf1/cip1 and p27^kip1. WPC also suppressed HG-induced p38 mitogen-activated protein kinase (p38 MAPK) and extracellular-signal-regulated kinase 1/2 (ERK 1/2) phosphorylation. Furthermore, WPC inhibited HG-induced production of dichlorofluorescein (DCF)-sensitive intracellular reactive oxygen species (ROS). In conclusion, HG promoted mesangial cell proliferation, and WPC inhibited this activity, at least in part, via induction of cell cycle arrest and activation of anti-oxidant properties. Taken together, these results suggest that P. cocos may be a potent regulator of HG-induced proliferation.

Endothelin-1 (ET-1) is a powerful vasoconstrictor that contributes to blood pressure elevation. The biological effects of ETs are mediated by two receptors, namely, endothelin type A receptor (ET_AR) and endothelin type B receptor (ET_BR). Chinese herbal medicines (CHM) with antagonist activity for these two receptors were screened by establishing stable clones of CHO-K1 cells expressing high levels of human ET_AR and ET_BR, namely CHO-ET_AR and CHO-ET_BR.The aqueous extract of Prunellae Spica (P1) inhibited the binding of ¹²⁵I-ET-1 to ET_AR and ET_BR in CHO-ET_AR and CHO-ET_BR cells, respectively. P1 suppressed the ET-1-induced mobilization of intracellular Ca²⁺. Through the alcohol fractionation of P1, the antagonists of human ET_AR and ET_BR were found to belong to different, separable ingredients and the antagonist of ET_AR is more soluble in alcohol. The two antagonists were also effective in the test on human primary cells, HASMC and HUVEC. P1 successfully prevented the development of ET-1-associated hypertension in rats without further purification. These results indicate the presence of anti-hypertensive ingredients in P. Spica extract, at least through the inactivation of ET_AR and/or ET_BR.

In the central nervous system inflammation is dependent upon the synthesis of various inflammatory mediators by local neurons, astrocytes and especially microglia. In this study, we investigated the anti-inflammatory activities of the semen extract of Thuja orientalis (Thujae Orientalis Semen; TOS) on transient middle cerebral artery occlusion (tMCAO)-induced ischemia in rats and the production of inflammatory mediators such as nitric oxide (NO), prostaglandin E₂ (PGE₂) and proinflammatory cytokine, interleukin (IL)-1β in lipopolysaccharide (LPS)-stimulated BV-2 mouse microglia. TOS extract significantly decreased the infarction volumes of ischemic brains and also inhibited microglia activation and neuronal death. In addition, TOS extract significantly decreased the production of NO, PGE₂ and IL-1β in LPS-stimulated BV-2 microglia. TOS extract also attenuated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and IL-1β mRNAs and proteins in activated microglia. Furthermore, TOS extract significantly suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK, and the nuclear translocation of NF-κB p65 in activated microglia. Our results indicate that TOS extract is capable of inhibiting microglia activation in an ischemic brain through the down-regulation of inflammatory responses, suggesting that the TOS extract may have therapeutic potential as an anti-inflammatory drug for ischemic stroke.

In this report, the anti-hepatitis B virus (HBV) activity of dehydrocheilanthifoline (DHCH), a quaternary ammonium alkaloid isolated from the traditional Chinese medicine Corydalis saxicola Bunting (Papaveraceae), was determined in vitro. Following six days of treatment, DHCH efficiently suppressed the secretions of HBsAg and HBeAg in HepG2.2.15 cell cultures, with a half-maximal inhibitory concentration (IC₅₀) of 15.84 and 17.12 μM, and with a therapeutic index (TI) of 7.32 and 6.77, respectively. Further studies revealed that DHCH reduced the levels of extracellular DNA, intracellular DNA and covalently closed circular DNA (cccDNA) of HBV in a dose-dependent and time-dependent manner, with IC₅₀ values of 15.08, 7.62 and 8.25 μM, respectively after six days of treatment. In contrast, the level of viral pre-genomic RNA (pgRNA) increased 6.13-fold after treatment with DHCH. Together, it was demonstrated for the first time that DHCH could significantly inhibit the replication of HBV, which warrants further studies on the antiviral mechanisms of DHCH, and suggests that it may be a promising candidate in the therapy of HBV infection.

Grifola frondosa (GF), a high value medicinal mushroom in China and Japan, is popularly consumed as traditional medicines and health foods, especially for enhancing immune functions. In this study, our aim was to examine the immunomodulatory activities of GF and its bioactive compound ergosterol peroxide (EPO) in lipopolysaccharide (LPS)-induced human monocytic (THP-1) cells. At low concentrations, EPO but not other extracts showed a full protection against LPS-induced cell toxicity. EPO significantly blocked MyD88 and VCAM-1 expression, and cytokine (IL-1β, IL-6 and TNF-α) production in LPS-stimulated cells. It also effectively inhibited NF-κB activation, which was further confirmed with siRNA treatment. These results conclude that EPO may play an important role in the immunomodulatory activity of GF through inhibiting the production of pro-inflammatory mediators and activation of NF-κB signaling pathway.

In the present study, active fractions of the methanolic extract of Xanthium strumarium (XS) showing potent cytotoxicity were determined using microculture tetrazolium (MTT) and sulforhodamine B (SRB) assays in selected cancer cell lines. The active fractions viz., chloroform soluble fraction of root (CEXSR), hexane soluble fraction of leaf (HEXSL), hexane soluble fraction of fruits (HEXSF) and chloroform soluble fraction of fruits (CEXSF) of XS were tested in transplantable animal tumor models for their antitumor potential. Dalton's ascitic lymphoma (DLA) cells were used to induce solid and liquid (ascites) tumor in mice. The tumor bearing animals were treated with active fractions at two dose levels (100 and 200 mg/kg). The antitumor activities of the active fractions in tumor bearing animals were monitored with parameters such as body weight and increase in life-span as well as biochemical and hematological modalities (in the case of liquid tumor). Tumor incidence and tumor volume were the parameters monitored in the case of the solid tumor model. The results were analyzed by one-way ANOVA followed by Tukey's post hoc test. The extracts were found to increase the life-span of tumor bearing animals and restore the altered hematological and biochemical parameters significantly.

Podophyllotoxin, a kind of lignan extracted from the Podophyllum plant, has been shown to inhibit the growth of various carcinoma cells. However, the molecular mechanism remains unclear. In this study, the inhibition of cell growth and changes in protein expression induced by podophyllotoxin were investigated in human cervical carcinoma HeLa cells. Our results demonstrate that Podophyllotoxin inhibits HeLa cell growth and induces apoptosis. By using proteomic techniques, seven proteins were found to be significantly regulated by podophyllotoxin compared to the untreated control; among them, four were down-regulated and three were up-regulated. All of the seven proteins were identified with peptide mass fingerprinting using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) after in-gel trypsin digestion. Five of these proteins are involved in protein metabolism, and the other two play roles in cell communication and signaling transduction pathways. It is suggested that the effect of podophyllotoxin on the growth of tumor cells is significantly related to the metabolism-associated proteins.

Oridonin, a natural tetracycline diterpenoid isolated from Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide variety of tumors. However, its effect on highly metastatic breast cancer cells has not been addressed. In this study, we investigated the effects of oridonin on growth, migration and invasion of highly-metastatic human breast cancer cells. Our results showed that oridonin induced potent growth inhibition on human breast cancer cells MCF-7 and MDA-MB-231 in a time- and dose-dependent manner. According to the flow cytometric analysis, oridonin suppressed MCF-7 cell growth by cell cycle arrest at the G2/M phase and caused accumulation of MDA-MB-231 cells in the Sub-G1 phase. The induced apoptotic effect of oridonin was further confirmed by a morphologic characteristics assay and TUNEL assay. Oridonin triggered the reduction of Bcl-2/Bax ratio, caspase-8, NF-κB (p65), IKKα, IKKβ, phospho-mTOR, and increased expression level of cleaved PARP, Fas and PPARγ in a time-dependent manner. Immunofluorescent analysis showed that γH2AX-containing nuclear foci were significant in oridonin-treated MDA-MB-231 cells. Meanwhile, oridonin significantly suppressed MDA-MB-231 cell migration and invasion, decreased MMP-2/MMP-9 activation and inhibited the expression of Integrin β1 and FAK. In conclusion, oridonin inhibited the growth and induced apoptosis in breast cancer cells, which might be related to DNA damage and activation of intrinsic or extrinsic apoptotic pathways. Moreover, oridonin also inhibited tumor invasion and metastasis in vitro possibly via decreasing the expression of MMPs and regulating the Integrin β1/FAK pathway in MDA-MB-231 cells.

Natural product Tanshinone IIA (TanIIA) induces apoptosis and differentiation in hepatocellular carcinoma (HCC) cells, but its clinical use is limited due to poor water solubility and lack of appropriate formulations for drug delivery. In this study, we capsulated TanIIA into a microemulsion (ME) that was composed of phospholipid, ethyl oleate, glycerol and pluronic F68. We then determined the anticancer effects and mechanisms of action for TanIIA ME with in vitro and in vivo HCC models. The mRNA and protein levels of apoptosis-related molecules (Bcl-2, Bax and caspase-3) were analyzed in murine hepatoma H22 cells and H22 tumor-bearing mice by flow cytometry, RT-PCR and immunofluorescence staining. Compared with the groups treated with empty ME and drug solution, the mRNA levels of Bax and caspase-3 were up-regulated, and the mRNA and protein levels of Bcl-2 were down-regulated in H22 cells treated with TanIIA ME in a dose-dependent manner. The mRNA and protein levels of Bax and caspase-3 were up-regulated and the Bcl-2 levels were also down-regulated in animals treated with TanIIA ME in a dose-dependent manner. Our results suggest that as a novel drug delivery system, microemulsion enhances the antitumor effects of TanIIA.

A new, simple, accurate and reliable full-time five-wavelength fusion method for the simultaneous separation and determination of nine active chemical compositions (liquiritin apioside, liquiritin, isoliquiritin apioside, ononin, isoliquiritin, liquiritigenin, calycosin, isoliquiritigenin, Glycyrrhizic acid monoammonium salt) in traditional Chinese medicine Glycyrrhiza was developed using reverse phase high-performance liquid chromatography (RP-HPLC) coupled with a diode-array detector (DAD). The chromatographic separation was performed on an Agilent TC-C18 column with gradient elution using 0.04% methanoic acid (A) and acetonitrile (B) at a flow rate of 1.0 mL min^-1 and UV detection at 248 nm, 250 nm, 276 nm, 362 nm, 370 nm. The standard curves were linear over the range of 2.1379–12.8272 μg for liquiritin apioside, 3.9299–23.5794 μg for liquiritin, 1.0432–6.2592 μg for isoliquiritin apioside, 0.8764–5.8584 μg for ononin, 1.0701–6.4205 μg for isoliquiritin, 1.3685–8.2111 μg for liquiritigenin, 0.3927–2.3563 μg for calycosin, 0.2498– 1.4986 μg for isoliquiritigenin, 2.0094–12.0564 μg for Glycyrrhizic acid monoammonium salt, respectively (r² > 0.9997). The recoveries and relative standard deviation (RSD) varied from 95.09% to 103.54% and 1.09% to 2.36%, respectively. The precision for all the analytes was less than 2.52%. The method indicated good performance in terms of precision, accuracy and linearity. The method enabled the simultaneous determination of nine active chemical compositions for quality control of Glycyrrhiza.

In this paper, a useful method for screening and analyzing the potential bioactive components from Reduning Injection was developed using macrophage cell extraction and ultra-high performance liquid chromatography coupled with Q-TOF/MS spectrometry. In addition, the protective effects on macrophage cell damage induced by LPS in vitro were also investigated. The results showed that chlorogenic acid, 3, 4-dicaffeoylquinic acid, 3, 5-dicaffeoylquinic acid and 4, 5-dicaffeoylquinic acid significantly inhibited the prostaglandin E₂ (PGE₂) release and reversed the interleukin-6 (IL-6) secretion of macrophages (p < 0.05). These data indicated that the method of macrophage cell extraction coupled with UPLC-MS technology is feasible, rapid and useful for screening and analyzing potential bioactive components from TCM injection.