[Differential metabolites and metabolic pathways involving acupuncture-induced improvement of rheumatoid arthritis patients based on gas chromatography-mass spectrometry].

OBJECTIVE: To analyze the endogenous metabolic biomarkers and pathways in serum involving acupuncture-induced improvement of symptoms of patients with rheumatoid arthritis (RA) by using metabolomics technique. METHODS: A total of 30 RA patients who were treated in the Department of Acupuncture and Moxibustion of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine (from January 2018 to October 2018) were selected in the present study. They were randomly and equally divided into acupuncture group and medication group. Acupuncture (lifting-thrusting reinforcing and uniform reducing-reinforcing methods) was applied to bilateral Fengchi (GB20), Yangchi (TE4), Quchi (LI11), Yingu (KI10), Taixi (KI3), Xuehai （SP10）, Guanyuan (CV4), Yanglingquan (GB34) and Ashi-points for 20 min every time, once daily for 3 months. Patients of the medication group were asked to take Tripterygium Wilfordii Polyglycoside tablets (a positive drug for RA, one tablet per time, 3 times a day) for 3 months. Other 10 healthy volunteers were selected as the normal control group. The tenderness scale (0-4 points) and swelling scale (0-3 points) and morning stiffness time were recorded, and serum rheumatoid factor (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were detected for analyzing pharmacodynamic effects. Serum samples were captured for profiling and quantifying metabolite biomarkers by using GC-MS (gas chromatography-mass spectrometry) technique. The acquired metabolite profiles were processed (multivariable data analysis) by using ProteoWizard package, XCMS Online software and SIMCA 13.0 software, respectively, followed by screening differential metabolites according to variable importance projection (VIP) and by constructing metabolic pathways with MetaboAnalyst 4.0. RESULTS: After acupuncture treatment, the tenderness score, swelling score, morning stiffness time, serum RF and CRP contents were significantly decreased in both acupuncture and medication groups in comparison with their own pretreatment (P<0.05). No significant differences were found between acupuncture and medication groups in the levels of tenderness score, swelling score, morning stiffness time, serum RF and CRP contents (P>0.05). A total of 14 differential metabolites including citrate, creatine, 3-hydroxybutyrate arachidonic acid, arachidonic acid, valine, lactic acid and palmitic acid (up-regulated), and tryptophan, arginine, L-phenylalanine, glucose, glycine, glutamine, aspartic acid and (down-regulated) which mainly involve metabolic pathways of alanine, aspartic acid and glutamate; metabolism of phenylalanine, tyrosine and tryptophan; metabolism of glycine, serine and threonine; glyoxalic acid dicarboxylic acid metabolism; metabolism of starch and sucrose; and metabolism of phenylalanine and arachidonic acid, respectively.Citrate, creatine, arachidonic acid, valine and glucose was positively correlated with tenderness index, swelling index, morning stiff time, RF, CRF and ESR. Glycine, L-phenylalanine , glutamine was negatively correlated with efficacy indicators. CONCLUSION: Acupuncture can relieve symptoms of patients with RA, which may be related to its effects in improving amino acid metabolism and glucose metabolism.

Flavonoids Extraction from Propolis Attenuates Pathological Cardiac Hypertrophy through PI3K/AKT Signaling Pathway.

Propolis, a traditional medicine, has been widely used for a thousand years as an anti-inflammatory and antioxidant drug. The flavonoid fraction is the main active component of propolis, which possesses a wide range of biological activities, including activities related to heart disease. However, the role of the flavonoids extraction from propolis (FP) in heart disease remains unknown. This study shows that FP could attenuate ISO-induced pathological cardiac hypertrophy (PCH) and heart failure in mice. The effect of the two fetal cardiac genes, atrial natriuretic factor (ANF) and ß-myosin heavy chain (ß-MHC), on PCH was reversed by FP. Echocardiography analysis revealed cardiac ventricular dilation and contractile dysfunction in ISO-treated mice. This finding is consistent with the increased heart weight and cardiac ANF protein levels, massive replacement fibrosis, and myocardial apoptosis. However, pretreatment of mice with FP could attenuate cardiac dysfunction and hypertrophy in vivo. Furthermore, the cardiac protection of FP was suppressed by the pan-PI3K inhibitor wortmannin. FP is a novel cardioprotective agent that can attenuate adverse cardiac dysfunction, hypertrophy, and associated disorder, such as fibrosis. The effects may be closely correlated with PI3K/AKT signaling. FP may be clinically used to inhibit PCH progression and heart failure.

Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss.

The sigma-1 receptor, which is expressed throughout the brain, provides physiological benefits that include higher brain function. The sigma-1 receptor functions as a chaperone in the endoplasmic reticulum and may control cell death and regeneration within the central nervous system. Cutamesine (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl) piperazine dihydrochloride) is a ligand selective for this receptor and may mediate neuroprotective effects in the context of neurodegenerative disease. We therefore assessed whether cutamesine protects the inner ear from noise-induced or aging-associated hearing loss. Immunohistochemistry and Western blotting revealed that the sigma-1 receptor is present in adult cochlea. We treated mice with 0, 3, or 30 mg/kg cutamesine from 10 days before noise exposure until the end of the study. All subjects were exposed to a 120-dB, 4-kHz octave-band noise for 2 hr. We assessed auditory thresholds by measuring the auditory-evoked brainstem responses at 4, 8, and 16 kHz, prior to and 1 week, 1 month, or 3 months following noise exposure. For the aging study, measurements were made before treatment was initiated and after 3 or 9 months of cutamesine treatment. Damage to fibrocytes within the cochlear spiral limbus was assessed by quantitative histology. Cutamesine significantly reduced threshold shifts and cell death within the spiral limbus in response to intense noise. These effects were not dose or time dependent. Conversely, cutamesine did not prevent aging-associated hearing loss. These results suggest that cutamesine reduces noise-induced hearing loss and cochlear damage during the acute phase that follows exposure to an intense noise.