Effects of Viscum coloratum (Kom.) Nakai on collagen-induced rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Viscum coloratum (Kom.) Nakai has been traditionally used in China for nearly a thousand years to treat rheumatic diseases. However, its efficacy and mechanisms in treating rheumatoid arthritis (RA) have not been demonstrated. AIM OF THE STUDY: To investigate the anti-arthritic effects and molecular mechanisms of Viscum coloratum (Kom.) Nakai on collagen-induced arthritic mice through network pharmacology technology and experimental validation. MATERIALS AND METHODS: First, the main ingredients of the extract of Viscum coloratum (Kom.) Nakai (EVC) were identified through chemical composition characterization using Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS). Then, the collagen-induced arthritis (CIA) model was established in DBA/1 J mice and the ameliorative effects of EVC on the progression of CIA mice were evaluated by oral treatment with different doses of the EVC for 28 days. After that, cytokine antibody microarray assay was used to detect the levels of multiple inflammation-related cytokines and chemokines in each group, and performed Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichment analysis. Subsequently, the potential target for the effective chemical components of EVC in treating RA was identified using various databases. Additionally, a drug-disease target protein-protein interaction network (PPI) was conducted using Cytoscape for visualization and clustering, while GO and KEGG enrichment analyses were performed with the Metascape database. Finally, identified phenotypes and targets by network pharmacology analysis were experimentally validated in vivo. RESULTS: Treatment with EVC significantly suppressed the severity of CIA with a dramatic reduction of paw swelling, arthritis index, levels of IgGs (IgG, IgG1, IgG2a, and IgG2b), multi-inflammation-related cytokines and chemokines on the progression of CIA. Histopathological examinations showed EVC could markedly inhibit inflammatory cell infiltration, tartrate-resistant acid phosphatase (TRAP) activity of osteoclast, and bone destruction. Furthermore, GO and KEGG enrichment analyses revealed that EVC could ameliorate RA by inhibiting osteoclast differentiation and regulating multiple signaling pathways including Osteoclast differentiation, IL-17, and TNF. PPI network analysis demonstrated that AKT1, MMP9, MAPK3, and other genes were highly related to EVC in treating RA. Finally, we proved that EVC could inhibit the expression of NFTAc1, MMP9, Cathepsin K, and AKT which were closely related to osteoclast activity. CONCLUSIONS: EVC could treat RA through multiple components, multiple targets, and multiple pathways. The present study demonstrated the therapeutic efficacy of EVC and its molecular mechanisms in treating RA, indicating that it would be a potent candidate as a novel botanical drug for further investigation.

Efficacy of Hypertonic Dextrose Proliferation Therapy for the Treatment of Rotator Cuff Lesions: A Meta-Analysis.

Background: One of the most prevalent disorders of the shoulder is rotator cuff tendinosis, which is a major contributor to shoulder discomfort and shoulder joint dysfunction. Rotator cuff tendinosis occurs in 0.3% to 5.5% of people worldwide and is diagnosed in 0.5% to 7.4% of people in China annually. We performed a meta-analysis to assess whether hypertonic dextrose proliferation therapy, a form of prolotherapy, improves the well-being of patients with rotator cuff injuries. Methods: We screened the literature by searching the PubMed, Embase, Cochrane Library, and Web of Science databases for the search terms prolotherapy, hypertonic dextrose, and rotator cuff. We identified and evaluated studies that treated individuals with rotator cuff lesions with hypertonic dextrose proliferation therapy (intervention) or a placebo (control). The outcome measures for patients with rotator cuff lesions were the visual analog scale score, the shoulder pain and disability index, and other metrics. These metrics were used to evaluate the effects of hypertonic dextrose proliferation therapy on individuals with rotator cuff diseases by meta-analysis. Results: The meta-analysis used data from 6 studies. In the 6 studies, the visual analog scale scores improved in the intervention and control categories, with greater improvement for the intervention category compared with the control category (standardized mean difference [SMD], 1.10 [95% CI, 0.37-1.83]; P = .04). In the studies that measured other outcomes, greater improvement for the intervention category compared with the control category was seen for the shoulder pain and disability index score (SMD, 8.13 [95% CI, 5.34-10.91]; P < .01), flexion (SMD, 5.73 [95% CI, 0.99-10.47]; P < .01), and abduction (SMD, 6.49 [95% CI, 0.66-12.31]; P < .05). There were no statistically significant differences of internal rotation between the intervention and control categories (SMD, -1.74 [95% CI, -4.25 to 0.78]; P = .18) and external rotation (SMD, 2.78 [95% CI, -0.13 to 5.69]; P = .06). Conclusion: The findings of this study suggest that individuals with rotator cuff injuries may benefit from hypertonic dextrose proliferation therapy based on the visual analog scale score, the shoulder pain and disability index score, flexion, and abduction. These results must, nevertheless, be supported by high-caliber follow-up research.

Electroacupuncture Improves Learning and Memory Abilities via Activating AMPK/mTOR-Induced Autophagy in APP/PS1 Mice.

Alzheimer's disease (AD) has become a global public health problem characterized by memory and cognitive impairments. Electroacupuncture (EA) has been indicated to exert promising therapeutic effects on AD. This study aimed to further investigate the underlying mechanism of EA in AD treatment. APP/PS1 transgenic mice and wide-type mice underwent with or without EA treatment at GV20 and BL23 acupoints. Morris water maze test was utilized for examining the learning and memory of mice. Hematoxylin-eosin, Congo red, immunofluorescence, and TUNEL staining were employed for detecting the pathological changes of mouse brain hippocampus. Western blotting was implemented for measuring protein levels of autophagy- and AMPK/mTOR pathway-associated markers. APP/PS1 mice exhibited significant impairments in the spatial learning and memory. EA treatment improved the cognitive impairments, reduced amyloid-beta (Aß) deposition, and alleviated neuronal apoptosis in the hippocampal tissues of APP/PS1 mice. EA promoted autophagy and activated the AMPK/mTOR signaling pathway in the hippocampus of APP/PS1 mice. EA improves the cognitive deficits, enhances Aß clearance, and attenuates neuronal apoptosis in APP/PS1 mice in part by activating AMPK/mTOR-mediated autophagy.

Efficacy of acupuncture for sciatica: study protocol for a randomized controlled pilot trial.

BACKGROUND: Acupuncture is widely used for pain diseases while evidence of its efficacy for sciatica is insufficient. We aim to explore the feasibility and efficacy of acupuncture with different acupoint selecting strategies for sciatica induced by lumbar disc herniation. METHODS: This is a multicenter, three-arm, patient-assessor-blinded randomized controlled pilot trial. Ninety patients will be assigned randomly into 3 groups including disease-affected meridians (DAM) group, non-affected meridians (NAM) group, and sham acupuncture (SA) group in a 1:1:1 ratio. The trial involves a 4-week treatment along with follow-up for 22 weeks. The primary outcome is the change of leg pain intensity measured by the visual analogue scale (VAS) from baseline to week 4 after randomization. Secondary outcomes include functional status, back pain intensity, and quality of life. Adverse events will also be recorded. DISCUSSION: The results will inspire the optimal acupuncture strategy for sciatica and help establish a better design as well as power calculation for a full-scale study. TRIAL REGISTRATION: ChiCTR2000030680 (Chinese Clinical Trial Registry, http://www.chictr.org.cn , registered on 9 March 2020).

[Effects on cervical spondylosis of vertebral artery type and the concentrations of plasma NPY and UII in the patients treated with the modified acupuncture at unilateral/bilateral Renying (ST 9)].

OBJECTIVE: To observe the differences in the clinical therapeutic effects on cervical spondylosis of vertebral artery type (CSA) between the modified acupuncture and the routine acupuncture at unilateral/bilateral Renying (ST 9) as well as the impacts on the concentrations of plasma neuropeptide Y (NPY) and urotensinⅡ(UⅡ) in the patients. METHODS: A total of 160 patients were divided into a modified bilateral acupuncture group, a modified unilateral acupuncture group, a routine bilateral acupuncture group and a routine unilateral acupuncture group, 40 cases in each one according to the random number table. In the modified bilateral acupuncture group, the modified acupuncture was applied bilaterally to Renying (ST 9). In the modified unilateral acupuncture group, the modified acupuncture was applied unilaterally to Renying (ST 9). In the routine bilateral acupuncture group, the routine acupuncture was applied bilaterally to Renying (ST 9). In the routine unilateral acupuncture group, the routine acupuncture was applied unilaterally to Renying (ST 9). The treatment was given once every day, continuously for 6 days as one course. Two courses of treatment were required at the interval of 1 day. In each group, before and after treatment, we observed the peak systolic blood flow velocity (Vs) of the vertebral artery (VA) and the basilar artery (BA), cervical vertigo symptoms and functional assessment scales (ESCV) and the concentration of plasma NPY and UⅡ. The clinical therapeutic effects were compared among the groups. RESULTS: After treatment, the clinical therapeutic effect in the modified bilateral acupuncture group was 90.0% (36/40), which was better than 80.0% (32/40) in the modified unilateral acupuncture group, 77.5% (35/40) in the routine bilateral acupuncture group and 65.0% (26/40) in the routine unilateral acupuncture group (all P<0.05). After treatment, Vs of VA and BA was improved remarkably in every group (all P<0.01), and the result in the modified bilateral acupuncture group was higher than those in the other groups (all P<0.01). After treatment, ESCV scores were all increased remarkably in every group (all P<0.01). ESCV score and improvement index in the modified bilateral acupuncture group were all higher than those in the other groups (P<0.05, P<0.01). After treatment, the concentrations of plasma NPY and UⅡ were all reduced remarkably in every group (all P<0.01) and the differences were significant among the groups (all P<0.01). CONCLUSION: The modified bilateral acupuncture at Renying (ST 9) effectively regulates the blood supply of the vertebral basilar artery and improves the cerebral circulation. The effects are superior to those of the unilateral acupuncture at Renying (ST 9).

[Efficacy of Modified Acupuncture Method at Renying (ST 9) for Patients with Cervical Spondylosis of Vertebral Artery Type and Its Impact on Velocity of Cervical Blood Flow].

OBJECTIVE: To observe the clinical efficacy of modified acupuncture at Renying point (ST 9) for patients with cervical spondylosis of vertebral artery type and its influence on velocity of cervical blood flow. METHODS: Fifty-nine cases of vertebral artery type cervical spondylosis were randomly divided into control group (n=30) and treatment group (n=29). Both groups were acupunctured at ST 9, with routine acupuncture technique used in the control group and modified technique in the treatment group, respectively. All cases received two courses of treatment, each course covered consecutive 6 once-per-day treatments. Before and after treatment, transcranial Doppler (TCD) was used to measure the systolic peak blood flow velocity (Vs) of left vertebral artery (LVA), right vertebral artery (RVA) and basilar artery (BA), and the scores of "cervical vertigo symptoms and functional assessment scale" (CVSFAS) were also assessed, separately. RESULTS: CVSFAS scoring, Vs of LVA, RVA and BA after treatment showed significant improvement compared with those before treatment (P<0.01, P<0.05). The efficacy of the treatment group in the above mentioned indexes was superior to that of the control group (P<0.05). The total effective rate of the treatment group was 93.1% (27/29), superior to 70.0% (21/30) of the control group (P<0.05). CONCLUSIONS: The modified acupuncture method at ST 9 is clinically effective in the treatment of cervical spondylosis of vertebral artery type via increasing the Vs of vertebral-basilar artery, improving the local blood circulation and relieving pain.

Protective effect of the herbal medicine Gan­fu­kang against carbon tetrachloride­induced liver fibrosis in rats.

The aim of the present study was to investigate the effect of a herbal medicine formula, Gan-fu-kang (GFK), on the treatment of liver fibrosis in rats and the mechanisms via which it exerts its effect. Liver fibrosis was induced in rats by subcutaneous injection of carbon tetrachloride (CCl4) at 0.5 mg/kg body weight, twice a week for 8 weeks. The rats were randomly selected to receive saline or GFK at 31.25, 312.5 or 3,125 mg/kg body weight/day between weeks 9 and 20. An additional group of rats without CCl4 injection was used as the baseline. In the liver fibrosis model rats, an increase in plasma liver enzymes, fibrotic markers in serum and liver fibrosis, production of α-smooth muscle actin, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1, synthesis of collagen and activation of the Wnt/ß-catenin signaling pathway were observed. GFK administration was found to significantly reduce these changes. Results of this study demonstrate that GFK has a protective and therapeutic effect on liver fibrosis induced by CCl4, which may be associated with its inhibitory activity on HSC proliferation and collagen synthesis, effectively downregulating Wnt/ß-catenin signaling.

Protective effect of Astragalus polysaccharides on ATP binding cassette transporter A1 in THP-1 derived foam cells exposed to tumor necrosis factor-alpha.

Astragalus polysaccharide (APS), the main extract from the traditional Chinese medicinal herb Astragalus membranaceus, has been reported to benefit the treatment of immune-inflammatory diseases and metabolic disorders. In atherosclerotic plaques, proinflammatory cytokines exert adverse effects on lipids thereby aggravating atherosclerosis. Recent evidence shows that tumor necrosis factor-alpha (TNF-alpha) can down-regulate the expression of ATP-binding cassette transporter A1 (ABCA1), which plays a vital role in reverse cholesterol transport and determines the process of atherosclerosis. In the present study, the effects of APS on ABCA1 expression, cholesterol effluent rate and total cholesterol content of THP-1 derived foam cells exposed to TNF-alpha were investigated. Compared with the foam cells exposed to TNF-alpha, ABCA1 expression was promoted in the presence of APS. Consequently the cholesterol effluent rate increased and the total cholesterol content decreased significantly. TNF-alpha could enhance the activity of nuclear factor-kappa B (NF-kappaB) in the foam cells. This effect could be attenuated by APS. These findings suggest that APS could protect ABCA1 against the lesion of TNF-alpha in THP-1 derived foam cells, which may contribute to its antiatherosclerotic properties.