Electroacupuncture Pretreatment Ameliorates Anesthesia and Surgery-Induced Cognitive Dysfunction via Activation of an α7-nAChR Signal in Aged Rats.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) after anesthesia and surgery (AS) is a common complication in the elderly population. A cholinergic-dependent signal, the alpha7-nicotinic acetylcholine receptor (α7-nAChR), has been suggested to regulate cognitive processes in a variety of neurologic diseases. In the current study, we determined whether electroacupuncture (EA) pretreatment ameliorates AS-induced POCD in aged rats, as well as the underlying mechanism. METHODS: Male Sprague-Dawley rats (20 months old) were randomly assigned to the following 5 groups (n=12): vehicle; POCD (tibial fracture surgery); EA plus POCD; EA plus POCD and alpha-bungarotoxin (α-BGT); and POCD plus α-BGT groups. Alpha-bungarotoxin (1 µg/kg), a selective antagonist of α7-nAChR, was administrated via intraperitoneal injection before EA. Thirty days post-AS, the Morris water maze and a novel objective recognition test were used to evaluate cognitive function. Neuronal amount, apoptosis, microglial activation, percentage of high mobility group box 1 (HMGB1)- and nuclear factor-κB (NF-κB)-positive microglia, and levels of HMGB-1 downstream factors, including NF-κB, interleukin-6 (IL-6), and IL-1ß, were detected by Nissl staining, immunofluorescence, and Western blot assays. RESULTS: EA pretreatment significantly increased crossing platform times and elevated the time with a novel object, restored the quantity of neurons, decreased TUNEL-positive neurons, alleviated activation of microglia, downregulated expression of HMGB1 and NF-κB in the microglia, and reduced levels of phosphor-NF-κB, IL-6, and IL-1ß 35 days after AS, while α-BGT partially reversed these changes. CONCLUSION: EA pretreatment improved AS-induced POCD in aged rats, and the underlying mechanism may be associated with inhibition of HMGB1-NF-κB via an α7-nAChR signal in the microglia.

Effects of Transcutaneous Electrical Acupoint Stimulation on Postoperative Cognitive Decline in Elderly Patients: A Pilot Study.

BACKGROUND: Postoperative cognitive decline (POCD) in the old ages seriously delays the rapid recovery. Here, we aimed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) against POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, as well as the potential mechanism. METHODS: A prospective, single-center, parallel-group, randomized trial was designed. A total of 100 patients (age ≥65 years) undergoing laparoscopic radical resection of colon cancer were involved and randomly divided into TEAS (Group T) and control (Group C) groups. The patients in Group T were performed with percutaneous acupoint electrical stimulation in bilateral Hegu, Neiguan and Zusanli points from 30 minutes before anesthesia induction to the end of surgery. A Z-score based on Mini-Mental State Exam (MMSE) was used to assess the incidence of POCD. The levels of serum IL-6, hs-CRP, CGRP at 0 min before TEAS (T0), 1 h after beginning of surgery (T1) and the end of surgery (T2) were evaluated. RESULTS: Our data showed that the cumulative duration of POCD on postoperative day 2 and 3 in Group T was significantly decreased compared to Group C (P < 0.05). Compared with T0, the levels of serum IL-6, hs-CRP, and CGRP in both Group T and C were statistically elevated at T1 and T2 (P < 0.05). Moreover, the levels of serum IL-6 and hs-CRP were decreased, but the level of CGRP was increased in Group T compared to Group C at T1 and T2 (P < 0.05). CONCLUSION: TEAS is associated with a lower cumulative duration of POCD in elderly patients undergoing laparoscopic radical colon cancer surgery, which may be related to the regulation of inflammatory factors and neuropeptides interacted with gut-brain axis.

Novel Protein Tyrosine Phosphatase 1B Inhibitor-Geranylated Flavonoid from Mulberry Leaves Ameliorates Insulin Resistance.

Mulberry leaf is a common vegetable with a variety of beneficial effects, such as hypoglycemic activity. However, the underlying mechanism of its hypoglycemic effect have not been fully revealed. In this study, two flavonoid derivatives were isolated from mulberry leaves, a new geranylated flavonoid compound (1) and its structural analogue (2). The structures of compounds 1 and 2 were elucidated using spectroscopic analysis. To study the potential hypoglycemic properties of these compounds, their regulatory effects on protein tyrosine phosphatase 1B (PTP1B) were investigated. In comparison to oleanolic acid, compounds 1 and 2 showed significant inhibitory activities (IC50 = 4.53 ± 0.31 and 10.53 ± 1.76 µM) against PTP1B, the positive control (IC50 = 7.94 ± 0.76 µM). Molecular docking predicted the binding sites of compound 1 to PTP1B. In insulin-resistance HepG2 cell, compound 1 promoted glucose consumption in a dose-dependent manner. Furthermore, western blot and polymerase chain reaction analyses indicated that compound 1 might regulate glucose consumption through the PTP1B/IRS/PI3K/AKT pathway. In conclusion, geranylated flavonoids in mulberry leaves inhibite PTP1B and increase the glucose consumption in insulin-resistant cells. These findings provide an important basis for the use of mulberry leaf flavonoids as a dietary supplement to regulate glucose metabolism.