The American Journal of Chinese Medicine

Panax ginseng is one of the most frequently used herbs in the world. Numerous trials have evaluated its clinical benefits. However, the quality of these studies has not been comprehensively and systematically assessed. We reviewed randomized controlled trials (RCTs) of Panax ginseng to evaluate their quality and risk of bias. We searched four English databases, without publication date restriction. Two reviewers extracted details about the studies' methodological quality, guided by the Consolidated Standards of Reporting Trials (CONSORT) checklist and its extension for herbal interventions. Risk of bias was determined using the Cochrane Risk of Bias tool. Of 475 potentially relevant studies, 58 met our inclusion criteria. In these 58 studies, 48.3% of the suggested CONSORT checklist items and 35.9% of the extended herbal items were reported. The quality of RCTs published after the CONSORT checklist improved. Until 1995 (before CONSORT) (n = 4), 32.8% of the items were reported in studies. From 1996–2006 (CONSORT published and revised) (n = 30), 46.1% were reported, and from 2007 (n = 24), 53.5% were reported (p = 0.005). After the CONSORT extension for herbal interventions was published in 2006, RCT quality also improved, although not significantly. Until 2005 (n = 34), 35.2% of the extended herbal items were reported in studies; and from 2006 onwards (n = 24), 37.3% were reported (p = 0.64). Most studies classified risk of bias as "unclear". Overall, the quality of Panax ginseng RCT methodology has improved since the CONSORT checklist was introduced. However, more can be done to improve the methodological quality of, and reporting in, RCTs.

The constitution of traditional Chinese medicine was established in 1970s by Chinese scholars, in which the constitutions of Chinese people were classified into nine types for study. The phlegm-dampness constitution is one of the nine constitutions and is the most common type in constitution study. Genomics studies found four upregulated genes: COPS8, GNPDA1, CD52 and ARPC3; and six downregulated genes: GSPT2, CACNB2, FLJ20584, UXS1, IL21R and TNPO in the phlegm-dampness constitution. Gene functional analyses on genes affecting the differences between the phlegm-dampness constitution and the balanced constitution indicated that people with phlegm-dampness constitution were susceptible to hyperlipemia and diabetes. Results of epidemiological surveys also revealed that people with phlegm-dampness constitution have a much higher risk of obesity, metabolic syndrome, hypertension and diabetes than people with a balanced constitution. Therefore, differentiation of phlegm-dampness constitution could be performed in the normal population with the Constitution of Chinese Medicine Scale to estimate the risks of those diseases for prediction. For people with phlegm-dampness constitution, Chinese medicine could be used to reduce risk of related diseases. Constitution-based strategies in disease prevention and treatment are consistent with the current proposed 4P medical mode (personalized, predictive, preventive and participatory). With the rising burden of global disease and increasing medical expenditure, the objectives of medicine are transforming from treatment to prevention. Thus, studies on the phlegm-dampness constitution of traditional Chinese medicine are significantly important for the prediction and prevention of related diseases and maintenance of human health.

Rheumatoid arthritis (RA) is the most common chronic inflammatory disease with unknown causes and unknown cures in Western medicine. This double-blinded study aimed to investigate the efficacy and safety of a widely used traditional Chinese medicine (Paeoniflorin (PAE) plus cervus and cucumis polypeptide injection (CCPI) using disease-modifying antirheumatic drugs (DMARD) as a control (methotrexate (MTX) plus leflunomide (LEF)). Patients were randomly assigned to one of the three groups: PAE + CCPI, MTX + LEF, and MTX + LEF + CCPI. The primary end point was the American College of Rheumatology 20% improvement response criteria (ACR20). The secondary end point was that of adverse effect frequencies and the speed of onset action. Our results showed that more patients in the CCPI-containing groups responded to the ACR20 during early treatment. After six months, ACR20 showed no significant difference among the three treatments. The maximum improvement in the two DMARD groups was significantly higher than that in the PAE + CCPI group (p < 0.01). CCPI made the onset action of the DMARD therapy 4.6 times faster. PAE + CCPI had significantly lower adverse event incidences than the two DMARD groups. These results indicate that PAE + CCPI appear to be a more acceptable alternative to DMARDs when patients cannot use DMARDs. CCPI appears to be a beneficial add-on to DMARDs that makes the onset of action faster, especially when patients need to relieve RA symptoms as soon as possible. Although not as effective as DMARDs, PAE appears to be a safer option to substitute DMARDs for long-term RA treatment when DMARD toxicity is an issue.

This study aimed to examine the factors associated with Chinese medicine use amongst a sample of 10,287 Australian women aged 56–61 years. Data was obtained from a cross-sectional postal questionnaire conducted in 2007, this being the fifth survey of the Australian Longitudinal Study on Women's Health. This representative sample of 10,287 women was randomly selected from the Health Insurance Commission (Medicare) database. The outcome measure was the use of Chinese medicine in the previous 12 months. The predictive factors included demographics, health status measures and health service utilization measures. Statistical analyses included univariate chi-square and ANOVA tests and backward stepwise multiple logistic regression modelling. The use of Chinese medicine amongst women aged 56–61 years appears to be strongly influenced by their country of birth, consultation with a range of CAM practitioners, and the use of some self-prescribed CAM. Interestingly, severe tiredness was the only symptom or diagnosis that predicted Chinese medicine use. Given the substantial prevalence of Chinese medicine use and the finding that the use of Chinese medicine is heavily integrated alongside the use of many other CAM and conventional treatments, it is imperative for the safety of patients that health professionals (across complementary and conventional healthcare) fully recognise the possible Chinese medicine use amongst their practice populations. In order to help inform relevant practice and policy development it is also important that future research further examining women's decision-making, motivations and evaluations regarding Chinese medicine use considers such issues within the context of broader CAM and conventional health care utilization.

To determine whether the maternal administration of Wu-Ling-San during pregnancy affects amniotic fluid volume, we measured the fluid levels in pregnant women who either had or hadn't been administrated Wu-Ling-San. We investigated 504 amniotic pocket (AP) measurements in 61 healthy pregnant women, 437 AP measurements in 71 untreated pregnant women who exhibited pretibial edema during pregnancy, and 82 AP measurements in 21 pregnant women who exhibited pretibial edema during pregnancy and were treated with Wu-Ling-San therapy (Goreisan, 7.5 g/day). Among the 3 groups, differences in AP were not observed prior to 35 weeks of gestation. After 36 weeks of gestation, AP measures were significantly higher in the Wu-Ling-San-treated group (3.78 ± 0.81 cm), compared to the untreated group (3.34 ± 0.79 cm) (p = 0.0036). We identified no significant AP differences between the Wu-Ling-San-treated and control groups. Our findings indicate that the administration of Wu-Ling-San to pregnant women with pretibial edema can prevent subsequent reductions in amniotic fluid volume. Thus, Wu-Ling-San may be helpful in the treatment of oligoamnios.

This study aims to examine electro-acupuncture stimulation (EA) assisted therapy with analysis of heart rate variability to understand autonomic nervous activity variability (ANAV) and to track the changes in female patients with constipation. The average ages were 42±12 years old. The participants were divided by a single-blind and randomized trial into two groups: the electro-acupuncture-point group, and the non-electro-acupuncture-point group. Both of the groups had eight treatments, once a week. For the electro-acupuncture (EA) group, needles were inserted into their Zusunli (ST36), Shangiuxu (ST37), Tiensu (ST25), Shueidao (ST28), Guanyuan (CV4) and Qihai (CV6) points. For the sham electro-acupuncture (SA) group, needles were inserted into acu-points that were not the ones mentioned for the EA group. While inserting needles, needles were inserted lightly into the participants' skin and removed quickly (mock Transcutaneous Electrical Nerve Stimulation, TENTS). After an eight-week treatment period, the autonomic nervous system activities of the SA group did not show significant differences in their heart rate variability. However, the autonomic nervous system activities of the EA group had continuously increased after each session. The normalized high frequency powers (nHFP) of their autonomic nervous system activities were 26.79 in the first week, and they increased to 32.28 in the fourth week. In the eighth week, their nHFP had increased to 37.60 (p < 0.05). The normalized low frequency power (nLFP) was 30.81 in the first week. However, it decreased to 25.98 after three weeks of treatment. After the eight-week treatment period, the nLFP decreased to 24.84 (p < 0.05). After the eight-week treatment, the control group did not appear to undergo any physiological change, while the constipation had been improved for the experimental group. It was found that the activation of parasympathetic nervous system in the experimental group increased after the eight-week treatment. The effects of such a result on the enhancement of the activation of parasympathetic nervous system and the improvement of constipation should be further discussed.

Previous studies suggest baicalein, in addition to its antioxidant effects, protects against hypoxia/reoxygenation injury via its pro-oxidant properties. We hypothesize that a brief period of baicalein treatment prior to ischemia/reperfusion (I/R) may trigger preconditioning protection via a mitochondrial pro-oxidant mechanism. Using an established chick cardiomyocyte model of I/R, cells were preconditioned with baicalein (10 μM) for 10 min followed by 10-min wash prior to I/R. Intracellular oxidants were measured using 2′, 7′-dichlorofluorescin diacetate (DCFH/DA). Cell viability was assessed by propidium iodide and apoptosis determined by DNA fragmentation. Baicalein induced a transient but significant increase of DCF fluorescence within the 10-min preconditioning period, and led to significant reduction of cell death (38.9 ± 1.8% vs. 58.7 ± 1.2% in I/R control, n = 6, p < 0.001) and DNA fragmentation after I/R. Cotreatment with N-acetylcysteine (500 μM), mitochondrial complex III electron transport chain inhibitor myxothiazol (1 μM), mitochondrial K_ATP channel blocker 5-hydroxydecanoate-Na (5-HD, 500 μM) or anion channel inhibitor 4′, 4′-diisothiocyanato-stilbene-2, 2′-disulfonic acid (DIDS, 200 μM) resulted in significant abrogation of oxidant increase during induction as well as the protection conferred by baicalein preconditioning. These results suggest that baicalein preconditioning exhibits significant anti-apoptotic protection against cardiomyocyte I/R injury by mitochondrial oxidant signaling, which was in part mediated by mitochondrial K_ATP channel and anion channel opening.

The purpose of this study was to assess the efficacy of zishentongluo (ZSTL) for the treatment of diabetic nephropathy (DN) and its related mechanisms. Forty-five patients with DN were randomized to receive either ZSTL (n = 25) or benazepril (n = 20), an angiotensin converting enzyme inhibitor, for 12 weeks. Conventional biochemical tests were performed to determine fasting blood glucose (FBG), glycated hemoglobin (HbA1c), serum creatinine (SCr), endogenous creatinine clearance rate (Ccr), total cholesterol (TC), and triglyceride (TG) levels. The urinary albumin excretion rate (UAER), and endothelin 1 (ET-1), and atrial natriuretic peptide (ANP) levels were determined with a radioimmunoassay, and vascular endothelial growth factor (VEGF) was detected using an enzyme-linked immunosorbent assay. The primary endpoint was change from the baseline to post-treatment in HbA1c. Secondary endpoints were change from baseline to post-treatment in FBG, TC, TG, UAER, SCr, Ccr, VI-C, ANP, ET-1, and VEGF. ZSTL was significantly more effective at improving the primary (i.e., HbA1c) and secondary (i.e., FBG, TC, TG, UAER, SCr, ANP, ET-1, and VEGF) outcomes than benazepril (p < 0.05). These findings suggest that ZSTL is superior to benazepril at improving the metabolic and renal functioning in patients with early-stage DN, in part, by modifying ANP, ET-1, and VEGF.

To examine the preventive and therapeutic effects of ginsenoside Rb1 for neural injury during cerebral infarction, we used a middle cerebral artery occlusion (MCAO) model in rats to investigate the effects of ginsenoside Rb1 with Edaravone as a control. Ginsenoside Rb1 was given to the rats by intragastric administration either before or after the MCAO surgery to study its preventive and therapeutic effects. Ginsenoside Rb1-treated rats had a smaller infarct volume than the positive control. Interleukin-1 (IL-1), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), neurofilament (NF) and growth associated protein-43 (GAP-43) were measured to determine brain damage and the recovery of nerves. These findings suggest that ginsenoside Rb1 has neuroprotective effects in rats, and the protection efficiency is higher than Edaravone. The protective mechanism is different from Edaravone. The preventive ability of ginsenoside Rb1 is higher than its repair ability in neuroprotection in vivo.

There is increasing evidence that starvation induces autophagy, which may be protective during starvation, in an AMPK-dependent manner. Polysaccharides from Fuzi (FPS) reportedly have protective effects on nutrition-limited livers. The present study was designed to determine whether FPS protected H9c2 cells against starvation-induced cytotoxicity using an AMPK/mTOR-dependent mechanism. H9c2 cells were incubated in serum and glucose starvation media for 12 hours to establish a cell injury model. 3-Methyladenine (3MA, an autophagy inhibitor) was used to identify the exact role of autophagy in starvation. Cells were incubated with different FPS concentrations, and the cell injury levels, autophagy activity and AMPK/mTOR phosphorylation were measured. Adenine 9-β-D-arabinofuranoside (Ara-A, an AMPK inhibitor) and 5-amino-4-imidazole-carboxamide riboside (AICAR, an AMPK activator) were used to identify whether the AMPK/mTOR pathway was involved in FPS-mediated cardioprotection. We demonstrated that starvation decreased cell viability in a time-dependent manner, and 3MA-induced autophagy inhibition aggravated the reduced cell viability. FPS treatment attenuated the cell viability decrement and the starvation-induced decline in the mitochondrial membrane potential (MMP), and autophagy; also, the AMPK/mTOR pathways were activated during treatment. Ara-A treatment abolished the protective effect of FPS, while AICAR treatment had a similar effect to FPS. We conclude that autophagy attenuates starvation-induced cardiomyocyte death, and FPS increases autophagy activity to protect against starvation-induced cytotoxicity in H9c2 cells, likely through AMPK/mTOR pathway activation.

Valproic acid (VPA), an anti-epileptic drug with a narrow therapeutic index, is a substrate of the monocarboxylate transporter (MCT). In this study, we investigated the effect of Gegen-Qinlian-Tang (GQT), a Chinese Medicine prescription containing Puerariae Radix (PR), Scutellariae Radix (SR), Coptidis Rhizoma (CR) and Glycyrrhizae Radix (GR), on the pharmacokinetics of VPA, as a probe drug of MCT, in rats and the underlying mechanism. Sprague–Dawley rats were orally administered VPA with and without GQT in crossover design. The serum concentrations of VPA were determined by a fluorescence polarization immunoassay. The results showed that coadministration with 2.0 and 4.0 g/kg of GQT remarkably decreased the C_max of VPA by 72% and 74% and reduced the AUC_0-t by 63% and 53%, respectively. The mechanism study using Caco-2 cells revealed that the uptake function of MCT was inhibited by GQT and each component herb. In conclusion, the MCT-mediated absorption of VPA was significantly decreased by GQT and its component herbs.

Rheumatoid arthritis (RA) has emerged as an important worldwide public health problem. Due to the lack of efficacy and major side effects related to many Western medical treatments, traditional Chinese medicine or herbal medicine is very often used to treat this disease. In the present study, we evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) in a rat model of RA induced by type-II collagen. Wistar rats with type-II collagen-induced arthritis (CIA) were given either 125 or 500 mg/kg of BCBE for RA. Paw swelling and weight were measured, and pathological joint sections of CIA rats were observed using the hematoxylin and eosin (HE) staining method. Protein and mRNA expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor κB (NF-κB) were determined by western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis in synovial tissue. During therapeutic treatment, BCBE significantly suppressed paw swelling, increased weight loss and ameliorated pathological joint changes. The protein and mRNA expressions of TLR4, MyD88 and NF-κB were downregulated in the CIA model when treated with BCBE. In conclusion, these results suggest that the treatment of RA with BCBE confers anti-RA activity and has therapeutic potential in this CIA model.

Cadmium (Cd²⁺) is an environmental contaminant that causes a variety of adverse effects. Auditory cells are sensitive to cadmium, and the cochlea is more vulnerable to cadmium toxicity than the other parts of the auditory system. Rosmarinic acid (RA) exhibits a wide spectrum of biological activities, mainly antioxidant and anti-inflammatory activities. However, the regulatory effects of RA in the auditory system have not been elucidated. In this study, we investigated the protective effects of RA on Cd²⁺-induced ototoxicity in vitro and ex vivo. The findings showed that RA inhibited Cd²⁺-mediated cell toxicity, reactive oxygen species generation, interleukin (IL)-6 and IL-1β production, the translocation of the apoptosis inducing factor into the nucleus and activation of caspases-3 in an auditory cell line, HEI-OC1. In addition, RA prevented the destruction of hair cell arrays in the rat organ of Cortiprimary explants in the presence of Cd²⁺. These results are expected to improve our understanding of the pharmacological mechanism of RA, and help develop potential therapeutic strategies against ototoxicity.

Actinidia callosa var. ephippioides (ACE) has been widely used to treat anti-pyretic, antinociceptive, anti-inflammation, abdominal pain and fever in Taiwan. This study aims to determine the mechanism of anti-inflammatory activities of ethyl acetate fraction of ACE (EA-ACE) using a model of λ-carrageenan (Carr)-induced paw edema in mouse model. In HPLC analysis, chemical characterization of EA-ACE was established. In order to investigate the anti-inflammatory mechanism of EA-ACE, we have detected the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the paw edema. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1β (IL-1β) were evaluated. Chemical characterization from HPLC indicated that EA-ACE contains betulinic acid, ursolic acid and oleanolic acid. In the anti-inflammatory test, EA-ACE decreased the paw edema after Carr administration, increased the activities of CAT, SOD, and GPx and decreased the MDA level in the edema paw at the 5th hr after Carr injection. EA-ACE affects the serum NO, TNF-α, and IL-1β levels at the 5th hr after Carr injection. EA-ACE decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions by Western blotting. Actinidia callosa var. ephippioides have the potential to provide a therapeutic approach to inflammation-associated disorders.

Cisplatin is commonly used as a chemotherapeutic agent against many human cancers. However, it generates reactive oxygen species (ROS) and has serious dose-limiting side effects, including ototoxicity. The roots of Curculigo orchioides (C. orchioides) have been used to treat auditory diseases such as tinnitus and hearing loss in Chinese traditional medicine. In the present study, we investigated the protective effects of an ethanol extract obtained from C. orchioides rhizome (COR) on cisplatin-induced cell damage in auditory cells (HEI-OC1). COR (2.5–25 μg/ml) inhibited cisplatin-induced HEI-OC1 cell damage in a dose-dependent manner. To investigate the protective mechanism of COR on cisplatin cytotoxicity in HEI-OC1 cells, we measured the effects of COR on ROS generation and lipid peroxidation in cisplatin-treated cells as well as its scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals. COR (1–25 μg/ml) had scavenging activities against superoxide radicals, hydroxyl radicals, hydrogen peroxide, and DPPH radicals, as well as reduced lipid peroxidation. In in vivo experiments, COR was shown to reduce cochlear and peripheral auditory function impairments through cisplatin-induced auditory damage in mice. These results indicate that COR protects from cisplatin-induced auditory damage by inhibiting lipid peroxidation and scavenging activities against free radicals.

An increasing number of cancer patients are using herbs in combination with conventional chemotherapeutic treatment. It is therefore important to study the potential consequences of the interactions between herbs and anticancer drugs. The effects of extracts from Panax ginseng (PGS) and Salvia miltiorrhiza Bunge (SMB) on the pharmacokinetics of 5-fluorouracil (5-FU) were performed in vivo and detected by high performance liquid chromatography (HPLC), while, an ATP assay was used to study the pharmacodynamic interactions in vitro. The results of the pharmacokinetic experiments showed a significant increase in the elimination half-life (t1/2(k_e)) of 5-FU in the PGS-pretreated group and in the area under the curve (AUC) in the SMB-pretreated group compared with the control group. However, after SMB pretreatment, weight loss was observed in rats. The results of pharmacodynamic experiments showed that neither PGS nor SMB, when used alone, directly inhibited cancer cell growth at 0.1–100 μg/ml. Moreover, PGS had a synergistic cytotoxic effect with 5-FU on human gastric cancer cells but not on normal gastric cells. The results imply that when combined with 5-FU, PGS may be a better candidate for further study. This study might provide insights for the selection of herbal-chemotherapy agent interactions.