Locus coeruleus tyrosine hydroxylase positive neurons mediated the peripheral and central therapeutic effects of transcutaneous auricular vagus nerve stimulation (taVNS) in MRL/lpr mice.

OBJECTIVE: This study aims to investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on the development of systemic lupus erythematosus (SLE) in MRL/lpr mice. METHODS: MRL/lpr mice were treated with taVNS for ten weeks. Locus coeruleus (LC) tyrosine hydroxylase positive (TH+) neurons were selectively lesioned by stereotactic injection of 6-hydroxydopamine (6-OHDA) or selectively activated by chemogenetic methods. Sympathetic denervation was conducted by intraperitoneal injection of 6-OHDA. RESULTS: TaVNS activated the TH + neurons in LC. TaVNS produced central therapeutic effects by reducing the number of hippocampal microglia, and increasing the number of surviving LC TH+ neurons in MRL/lpr mice. TaVNS also retarded the development of lymphadenectasis and splenomegaly, decreased the proportion of double-negative T (DNT) cells, and alleviated nephritis in MRL/lpr mice. The lesion of LC TH+ neurons eliminated both these central and peripheral therapeutic effects of taVNS, while chemogenetic activation of LC TH+ neurons mimicked most central and peripheral protective effects of taVNS in MRL/lpr mice. Furthermore, taVNS regulated the autonomic nervous system in MRL/lpr mice. CONCLUSION: This study provides direct evidence that taVNS can retard the development of peripheral and central symptoms of SLE, which is mediated by the LC TH+ neurons.

Efficacy and safety of traditional Chinese medicine for the treatment of epilepsy: A updated meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of Traditional Chinese Medicine (TCM) in the treatment of epilepsy. METHODS: A comprehensive search of the database in both Chinese and English was performed. Data from the selected studies were extracted and analyzed independently by two authors. RESULTS: 30 randomized controlled trials (RCTs) were included in the meta-analysis with a total of 2471 patients. Among them, 4 trials (n = 235) focused on TCM monotherapy, while the other 26 trials (n = 2236) assessed the benefit of TCM as an add-on therapy to antiseizure medications (ASMs). For the efficacy, the meta-analysis found (1) The effective rate in TCM monotherapy group was higher than that in control group (OR = 4.92, 95 % CI: 2.29-10.57, Z = 4.08, P 0.0001); (2) The add-on of TCM also increased the effective rate (OR = 3.37, 95 % CI: 2.65-4.30, Z = 9.85, P 0.00001) and seizure freedom rate (OR = 1.93, 95 % CI: 1.53-2.44, Z = 5.58, P 0.00001). In terms of safety, the add-on of TCM reduced the rate of total adverse events (OR = 0.46, 95 % CI: 0.31-0.67, Z = 3.96, P 0.0001) as well as adverse events of the gastrointestinal and nervous system. 26 different TCM prescriptions were used in these included RCTs. Among them, the 5 most frequently used herbs were Acorus tatarinowii (19 out of 26), Glycyrrhiza uralensis (13 out of 26), Gastrodia elata (12 out of 26), Pinellia ternata (11 out of 26) and Poria cocos (11 out of 26). CONCLUSION: This study suggested that TCM may be a relatively efficacious and safe clinical strategy for the treatment of epilepsy. Several limitations still exist, such as the risk of bias in the included studies, the diversified composition of TCM prescriptions, and the relatively low quality of study design.

Tripterygium wilfordii Hook F combination therapy with methotrexate for rheumatoid arthritis: An updated meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory arthropathy. Tripterygium wilfordii Hook F (TwHF) is common herbal medicine for the treatment of RA in China. However, many important issues, such as efficacy, safety and optimal doses of the combination therapy of TwHF and Methotrexate (MTX) for RA remain to be evaluated. AIMS OF THE STUDY: This study aims to evaluate the efficacy and safety of combination therapy of TwHF and MTX for RA by meta-analysis of randomized clinical trials (RCTs). MATERIAL AND METHODS: Relevant literature was searched from English (PubMed, Web of Science, EMBASE, and Cochrane library) and Chinese databases (WanFang, VIP, CNKI) until December 2021. Response rates and rates of adverse events (AEs) were independently extracted and analyzed. RESULTS: Fourteen randomized controlled trials (RCTs) were included with a total of 1446 patients, which included eight new RCTs with a total of 803 new patients when compared with the previous meta-analysis (Wang et al., 2017). Compared to MTX monotherapy, TwHF + MTX was revealed a higher effective rate (RR = 1.15, 95% CI: 1.10, 1.21), partial remission rate (RR = 1.27, 95% CI: 1.15, 1.40) and remission rate (RR = 1.31, 95% CI: 1.11, 1.55). The addition of TwHF benefited the clinical symptoms (such as tender joint count) and most laboratory indexes (such as the tumor necrosis factor-α). According to the subgroup analyses, the efficacy of the TwHF + MTX seems to be positively associated with the dose of TwHF (10 mg/d vs 30-60 mg/d), negatively related to the dose of MTX (∼10 mg/w vs ∼15 mg/w) and methodological risk of bias of included RCTs, and unrelated to the duration of therapy (12-week vs 24-week). For safety, the addition of TwHF did not increase the risk of most AEs and even reduced the risk of infection and liver AEs. CONCLUSION: Combining TwHF with MTX may be a superior strategy in the treatment of RA compared with MTX monotherapy. The optimal combination of TwHF + MTX therapy might be TwHF at 30-60 mg/d with MTX (∼10 mg/w). Further high-quality double-blind RCTs may be able to change the conclusions of our study, which are still warranted.