-Jin Zhang

The Role of Oxidative Stress and Antioxidants in Liver Diseases

A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

The effectiveness and safety of acupuncture therapy in depressive disorders: systematic review and meta-analysis

BACKGROUND Although acupuncture has been used as an alternative treatment for depressive disorders, its effectiveness and safety are not well defined. The purpose of this systematic review with meta-analysis was to evaluate the effectiveness of acupuncture as monotherapy and as an additional therapy in treating various depressive conditions, particularly major depressive disorder (MDD) and post-stroke depression (PSD). METHODS Following systematic review, meta-analysis was conducted on high-quality randomized controlled trials (RCTs). RESULTS Of 207 clinical studies of acupuncture for various depression retrieved, 113 (54.6%) were on MDD and 76 (36.7%) on PSD. Twenty RCTs of MDD (n=1998) and 15 of PSD (n=1680) identified for high-quality protocol (Jadad score >or=3) were included for meta-analysis. The efficacy of acupuncture as monotherapy was comparable to antidepressants alone in improving clinical response and alleviating symptom severity of MDD, but not different from sham acupuncture. No sufficient evidence favored the expectation that acupuncture combined with antidepressants could yield better outcomes than antidepressants alone in treating MDD. Acupuncture was superior to antidepressants and waitlist controls in improving both response and symptom severity of PSD. The incidence of adverse events in acupuncture intervention was significantly lower than antidepressants. CONCLUSIONS Acupuncture therapy is safe and effective in treating MDD and PSD, and could be considered an alternative option for the two disorders. The efficacy in other forms of depression remains to be further determined.

Neural Acupuncture Unit: A New Concept for Interpreting Effects and Mechanisms of Acupuncture

When an acupuncture needle is inserted into a designated point on the body and mechanical or electrical stimulation is delivered, various neural and neuroactive components are activated. The collection of the activated neural and neuroactive components distributed in the skin, muscle, and connective tissues surrounding the inserted needle is defined as a neural acupuncture unit (NAU). The traditionally defined acupoints represent an anatomical landmark system that indicates local sites where NAUs may contain relatively dense and concentrated neural and neuroactive components, upon which acupuncture stimulation would elicit a more efficient therapeutic response. The NAU-based local mechanisms of biochemical and biophysical reactions play an important role in acupuncture-induced analgesia. Different properties of NAUs are associated with different components of needling sensation. There exist several central pathways to convey NAU-induced acupuncture signals, Electroacupuncture (EA) frequency-specific neurochemical effects are related to different peripheral and central pathways transmitting afferent signals from different frequency of NAU stimulation. More widespread and intense neuroimaging responses of brain regions to acupuncture may be a consequence of more efficient NAU stimulation modes. The introduction of the conception of NAU provides a new theoretical approach to interpreting effects and mechanisms of acupuncture in modern biomedical knowledge framework.

Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: A double-blind, randomized, placebo-controlled study

BACKGROUND Previous studies suggest that the serotonin-3 (5-HT3) receptor antagonist ondansetron possesses the therapeutic potential for schizophrenia. This study was designed to determine whether ondansetron as an adjunct to haloperidol could enhance the clinical efficacy and reduce the adverse side effects in chronic treatment-resistant schizophrenia. METHODS Under double-blind, randomized conditions, 121 treatment-resistant inpatients with chronic DSM-IV-diagnosed schizophrenia received haloperidol (4-30 mg/day) combined with either placebo (N=63) or a fixed dose of 8 mg/day of ondansetron (N=58) for 12 weeks. Efficacy was defined as the change from baseline to endpoint in score on overall scale and subscales of the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression-Severity (CGI-S). Side effects were evaluated using the Treatment Emergent Symptom Scale and Extrapyramidal Symptom Rating Scale. RESULTS Ondansetron combined with haloperidol produced a significantly greater improvement on PANSS overall scale and subscales for negative symptoms, general psychopathology, and cognition at endpoint compared to placebo with haloperidol, but no between-treatment group difference was observed on the subscale for positive symptoms and CGI-S. The ondansetron-treated group had a significantly higher proportion of patients with a 30% or greater baseline-to-endpoint reduction in PANSS total score than placebo. Patients in adjunctive ondansetron therapy also experienced significantly lower incidence and severity of parkinsonism and akathisia as well as fewer behavioral hyperactivity, cardiac, and gastrointestinal side effects. CONCLUSIONS Ondansetron is an effective adjunctive agent in enhancing the effectiveness and reducing some adverse side effects of antipsychotic therapy for chronic, treatment-resistant schizophrenia, particularly for negative and cognitive symptoms.

Acupressure, reflexology, and auricular acupressure for insomnia: a systematic review of randomized controlled trials.

Previous randomized controlled trials (RCTs) have shown that acupuncture may be efficacious for insomnia. Instead of needling, acupressure, reflexology, and auricular acupressure are procedures involving physical pressure on acupoints or reflex areas. These variants of acupuncture are gaining popularity, perhaps due to their non-invasive nature. A systematic review has therefore been conducted to examine their efficacy and safety for insomnia. Two independent researchers searched five English and 10 Chinese databases from inception to May 2010. Forty RCTs were identified for analysis. Only 10 studies used sham controls, four used double-blind design, nine studies scored three or more by the Jadad scale, and all had at least one domain with high risk of bias. Meta-analyses of the moderate-quality RCTs found that acupressure as monotherapy fared marginally better than sham control. Studies that compared auricular acupressure and sham control showed equivocal results. It was also found that acupressure, reflexology, or auricular acupressure as monotherapy or combined with routine care was significantly more efficacious than routine care or no treatment. Owing to the methodological limitations of the studies and equivocal results, the current evidence does not allow a clear conclusion on the benefits of acupressure, reflexology, and auricular acupressure for insomnia.

Neuroprotective effects of atypical D1 receptor agonist SKF83959 are mediated via D1 receptor‐dependent inhibition of glycogen synthase kinase‐3β and a receptor‐independent anti‐oxidative action

3‐methyl‐6‐chloro‐7,8‐hydroxy‐1‐(3‐methylphenyl)‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine (SKF83959), a selective agonist for the putative phosphatidylinositol (PI)‐linked dopamine receptor (DAR), has been shown to possess potent anti‐Parkinson disease effects but produces less dyskinesia and motor fluctuation that are frequently observed in Parkinson disease drug therapies. The present study was designed to detect the neuroprotection of SKF83959 and its potential mechanism for the effect in cultured rat cortical cells. The presence of SKF83959 with a dose range of 0.1–30 μmol/L improved H2O2‐reduced cell viability in a dose‐dependent manner. The anti‐apoptotic action of SKF83959 was partially abolished by pre‐application of the D1 antagonist SCH23390 (30 μmol/L) and the PI 3‐kinase (PI 3‐K) inhibitor LY294002 but not by the MEK1/2 inhibitor PD98059 (30 μmol/L). Moreover, SKF83959 treatment significantly inhibited H2O2‐activated glycogen synthase kinase‐3β (GSK‐3β) which was associated with the drug’s neuroprotective effect, but this inhibition was attenuated by SCH23390 and a selective PI 3‐K inhibitor. Moreover, the application of either SKF83959 or a pharmacological inhibitor of GSK‐3β attenuated the inhibition by H2O2 on the expression of inducible NO synthase and production of NO. This indicates that D1‐like receptor, presumably PI‐linked D1 receptor, ‐mediated alteration of PI 3‐K/Akt/GSK‐3β pathway is involved in the neuroprotection by SKF83959. In addition, SKF83959 also effectively decreased the level of the lipid peroxidation and increased the activity of GSH‐peroxidase altered by H2O2. These results suggest that SKF83959 exerts its neuroprotective effect through both receptor‐dependent and independent mechanisms: Inhibition of GSK‐3β and consequently increasing the expression of inducible NO synthase via putative PI‐linked DAR; and its anti‐oxidative activity which is independent of DAR.

The herbal medicine Dipsacus asper Wall extract reduces the cognitive deficits and overexpression of β-amyloid protein induced by aluminum exposure

Excess aluminum (Al) exposure impairs neurocognitive function in humans and animals. Epidemiologic studies have shown a potential link between chronic Al exposure and Alzheimers disease. In the present study, we sought to evaluate the protective effects of the herbal medicine Dipsacus asper extract against the cognitive impairment and overexpression of hippocampal beta-amyloid protein (Abeta) induced by chronic Al exposure in rats. Vitamin E (VE) was used as a positive control. Following exposure to 0.3% aluminum chloride (AlCl(3)) solution for 90 days in their drinking water, animals displayed a striking decrease (>80%) in step-through latency in the passive avoidance task and a significant increase (123%) in the number of Abeta immunoreactive cells in the hippocampus compared to controls. Al-exposed animals were then randomly assigned to receive vehicle, Dipsacus asper extract (4 g/kg), or VE (40 mg/kg) treatment up to 5 months. Both Dipsacus asper extract and VE significantly ameliorated animals performance impairment in the passive avoidance task and suppressed the overexpression of hippocampal Abeta immunoreactivity. The effects of Dipsacus asper extract, but not VE, increased with time of treatment. The present results suggest that Dipsacus asper extract may possess therapeutic effects against Alzheimers disease.

Chinese herbal medicine for insomnia: A systematic review of randomized controlled trials

Chinese herbal medicine (CHM), either in single herb or in herbal formula, has been used to treat insomnia for more than 2000 years. A systematic review including Chinese and English literature of randomized controlled trials was conducted to examine the efficacy, safety, and composition of CHM for insomnia. Among the 217 studies we have reviewed, only eight had a Jadad score ≥3, and seven out of these eight studies had at least one domain with high risks of bias. Meta-analyses of the studies with Jadad score ≥3 found that CHM was similar to Western medication (three studies) and placebo (three studies) in treating insomnia. Due to the poor methodological quality of the studies and the small number of trials included in meta-analyses, the current evidence is insufficient to support the efficacy of CHM for insomnia. The frequency of adverse events associated with CHM was similar to that of placebo, but lower than with Western medication. Gui Pi Tang was the most commonly used standardized formula, while Suan Zao Ren (Ziziphus jujuba) was the most frequently used single herb. Further studies with a double-blind placebo-controlled design are needed to accurately determine the benefits and risks of CHM for insomnia.

A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia.

Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD) with bromocriptine (BMT), a dopamine agonist widely used for PRL-secreting disorders, in the treatment of risperidone-induced hyperprolactinemia. Twenty schizophrenic women who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 &mgr;g/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment with PGD (45 g/d) followed by BMT (5 mg/d) or BMT followed by PGD at the same doses for 4 weeks each, with an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients during PGD treatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals with schizophrenia.

Electroacupuncture for residual insomnia associated with major depressive disorder: a randomized controlled trial.

STUDY OBJECTIVES To evaluate the efficacy and safety of electroacupuncture as an additional treatment for residual insomnia associated with major depressive disorder (MDD). DESIGN Randomized, placebo-controlled. SETTING A psychiatric outpatient clinic. PARTICIPANTS 78 Chinese patients with DSM-IV-diagnosed MDD, insomnia complaint, a Hamilton Rating Scale for Depression (HDRS(17)) score ≤ 18, and fixed antidepressant dosage. INTERVENTION Electroacupuncture, minimal acupuncture (superficial needling at non-acupuncture points), or noninvasive placebo acupuncture 3 sessions weekly for 3 weeks. MEASUREMENTS AND RESULTS Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), HDRS(17), 1 week sleep diaries, and 3 day actigraphy were administered at baseline, 1 week post-treatment, and 4 week post-treatment. There was significant group by time interaction in ISI, PSQI, and sleep diary-derived sleep efficiency (mixed-effects models, P = 0.04, P = 0.03, and P = 0.01, respectively). Post hoc pairwise comparisons revealed that electroacupuncture and minimal acupuncture were more efficacious than placebo acupuncture in ISI and PSQI at 1 week and 4 week post-treatment. Minimal acupuncture resulted in greater improvement in sleep diary-derived sleep efficiency than placebo acupuncture at 1 week post-treatment. There was no significant between-group difference in actigraphy measures, depressive symptoms, daily functioning, and hypnotic consumption, and no difference in any measures between electroacupuncture and minimal acupuncture. CONCLUSION Compared with placebo acupuncture, electroacupuncture and minimal acupuncture resulted in greater improvement in subjective sleep measures at 1 week and 4 week post-treatment. No significant difference was found between electroacupuncture and minimal acupuncture, suggesting that the observed differences could be due to nonspecific effects of needling, regardless of whether it is done according to traditional Chinese medicine theory.