Clinical efficacy of Shugan granule in the treatment of mixed anxiety-depressive disorder: A multicenter, randomized, double-blind, placebo-controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Shugan granule is derived from Xiaoyao powder, a traditional Chinese medicine that has been shown to be effective in treating emotional disorders. At present, there is no standard drug treatment for mixed anxiety-depressive disorder (MADD), and no evidence-based clinical trial has been performed for any drug, meaning MADD patients are unable to obtain standardized treatment. AIM OF THE STUDY: The purpose of this clinical trial was to test the clinical efficacy and safety of Shugan granules in the treatment of MADD, and to provide clinical trial-based support along with drug recommendations for the treatment of MADD. MATERIALS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled study was conducted on 400 patients with MADD recruited from January 1, 2019 to December 31, 2020, and they were randomly divided into test and placebo groups with a 1:1 ratio. Subjects in the test group (n = 200) received oral administration of Shugan granules, while subjects in the placebo group (n = 200) received oral administration of a Shugan granule simulator. The treatment lasted for 8 weeks. The Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale-17 (HAMD-17), Clinical Global Impression Scale (CGIS), Self-rating Anxiety Scale (SAS), and Self-rating Depression Scale (SDS) were used to evaluate efficacy. In addition, the traditional Chinese medicine (TCM) syndrome scale for MADD was developed to observe improvements of related symptoms in patients after treatment based on the disease guidelines of TCM and the clinical manifestations of depression. Furthermore, the safety of Shugan granules was evaluated during and after treatment. RESULTS: After 8 weeks of treatment, the total scores for HAMA, HAMD, SAS, and SDS in the test group were significantly lower than those in the placebo group (P < 0.01). The proportion of patients with efficacy index (EI) > 1 for the CGIS score in the test group was significantly higher than that in the placebo group (P < 0.01). The efficacy of treatment in the test group based on the TCM syndrome scale was 70.16% and 88.27% after 4 weeks and 8 weeks, respectively, which was significantly higher than that in the placebo group (44.27% and 66.67% after 4 weeks and 8 weeks, respectively; P < 0.01). The disappearance rate of single symptoms in the test group was 20-30% higher than that in the placebo group, with a significant difference between groups (P < 0.05). During the treatment period, the incidence of adverse reactions was 2.05% in the test group and 2.06% in the placebo group, with no significant differences noted (P = 1.0000). CONCLUSION: Shugan granule was more effective than placebo in the treatment of MADD. Moreover, there was no significant difference between the two groups in terms of safety. This paper provides a clinical therapeutic regime using Shugan granule for the treatment of MADD.

Astragaloside IV improves angiogenesis under hypoxic conditions by enhancing hypoxia­inducible factor­1α SUMOylation.

Improving angiogenic capacity under hypoxic conditions is essential for improving the survival of skin grafts, as they often lack the necessary blood supply. The stable expression levels of hypoxia­inducible factor­1α (HIF­1α) in the nucleus directly affect the downstream vascular endothelial growth factor (VEGF) signaling pathway and regulate angiogenesis in a hypoxic environment. Astragaloside IV (AS­IV), an active component isolated from Astragalus membranaceus, has multiple biological effects including antioxidant and anti­diabetic effects, and the ability to provide protection from cardiovascular damage. However, the mechanisms underlying these effects have not previously been elucidated. The present study investigated whether AS­IV promotes angiogenesis via affecting the balance between ubiquitination and small ubiquitin­related modifier (SUMO) modification of HIF­1α. The results demonstrated that persistent hypoxia induces changes in expression levels of HIF­1α protein and significantly increases the proportion of dysplastic blood vessels. Further western blotting experiments showed that rapid attenuation and delayed compensation of SUMO1 activity is one of the reasons for the initial increase then decrease in HIF­1α levels. SUMO1 overexpression stabilized the presence of HIF­1α in the nucleus and decreased the extent of abnormal blood vessel morphology observed following hypoxia. AS­IV induces vascular endothelial cells to continuously produce SUMO1, stabilizes the HIF­1α/VEGF pathway and improves angiogenesis in hypoxic conditions. In summary, the present study confirmed that AS­IV stimulates vascular endothelial cells to continuously resupply SUMO1, stabilizes the presence of HIF­1α protein and improves angiogenesis in adverse hypoxic conditions, which may improve the success rate of flap graft surgery following trauma or burn.

Treatment of migraines with Tianshu capsule: a multi-center, double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3ß). METHODS: The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. RESULTS: One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. CONCLUSIONS: TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10.

Chinese herbal medicine Qinggongshoutao for the treatment of amnestic mild cognitive impairment: A 52-week randomized controlled trial.

INTRODUCTION: This randomized, double-blind trial aimed to test effect of a Chinese herbal medicine, Qinggongshoutao (QGST) pill, on the cognition and progression of amnestic mild cognitive impairment (aMCI). METHODS: Patients with aMCI were randomly assigned to receive QGST, Ginkgo biloba extract, or placebo for 52 weeks. The primary outcome measures were progression to possible or probable Alzheimer's disease (AD) and change in Alzheimer's Disease Assessment Scale-cognitive subscale scores; secondary outcome measures included assessments for cognition and function. RESULTS: Total 350 patients were enrolled, possible or probable AD developed in 10. There were significant differences in the probability of progression to AD in the QGST group (1.15%) compared with placebo group (10%). There was significant difference in Alzheimer's Disease Assessment Scale-cognitive subscale scores in favor of QGST over the placebo group. Secondary outcome measure (Mini-Mental State Examination) also showed benefit in QGST at end point. DISCUSSION: In patients with aMCI, QGST showed lower AD progression rate than placebo at 8.85%, and may have benefit on global cognition.