Targeting BDNF with acupuncture: A novel integrated strategy for diabetes and depression comorbidity.

Diabetes and depression are common comorbid conditions that impose a substantial health burden. Acupuncture may effectively improve symptoms in patients with diabetes and depression, but the underlying mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) may play a vital role in the effects of acupuncture on diabetes and depression comorbidity. This review summarizes the potential role of BDNF in acupuncture for diabetes and depression comorbidity. BDNF appears to exert its effects via the BDNF-TrkB-ERK-CREB signaling pathway. BDNF levels are reduced in diabetes and depression, and acupuncture may increase BDNF expression, improving symptoms and glycemic control. High-quality research is needed to validate the efficacy of acupuncture for diabetes and depression comorbidity. Randomized controlled trials and mechanistic studies should investigate the BDNF pathway and other potential mechanisms. Improved understanding of the links between diabetes, depression and acupuncture may enable targeted and individualized patient care. Earlier diagnosis and management of diabetes and depression comorbidity should also be a priority.

Acupuncture for Parkinson's disease-related constipation: current evidence and perspectives.

Parkinson's disease-related constipation (PDC) is commonly associated with impaired dopamine transmission and gastrointestinal dysfunction. Current pharmacological treatments have limited efficacy and potential side effects. Acupuncture has shown promise as an alternative or adjunct therapy by modulating the brain-gut axis, gastrointestinal hormones, and autonomic function. Preliminary randomized trials have shown that acupuncture significantly improves constipation symptoms, bowel movements, and comfort compared to sham or drug treatments and is well-tolerated. The mechanisms of action may involve regulating the gut microbiota and mucosal immunity to improve dysbiosis and gastrointestinal motility. However, more rigorous studies are required to optimize acupuncture protocols and determine long-term efficacy and safety. In summary, acupuncture shows promise as an adjunct therapy for PDC, but further research is needed to confirm its efficacy and safety.

Global trends and hotspots in research on acupuncture for stroke: a bibliometric and visualization analysis.

Acupuncture has been widely used in stroke and post-stroke rehabilitation (PSR), but there is no literature on the bibliometric analysis of acupuncture for stroke. This study aimed to characterize the global publications and analyze the trends of acupuncture for stroke in the past 40 years. We identified 1157 publications from the Web of Science Core Collection. The number of publications grew slowly in the first three decades from 1980 until it started to grow after 2010, with significant growth in 2011-2012 and 2019-2020. China, the USA, and South Korea are the top three countries in this field, and China has formed good internal cooperative relations. Early studies focused on the clinical efficacy of acupuncture for stroke. In the last five years, more emphasis has been placed on the effectiveness of acupuncture in treating sequelae and complications, combined with neuroimaging studies to explore the mechanisms of brain injury repair and neurological recovery. Acupuncture for stroke has a vast research potential, and researchers from different countries/regions and organizations still need to remove academic barriers to enhance communication and collaboration.

Opportunities and challenges of traditional Chinese medicine doctors in the era of artificial intelligence.

With the exponential advancement of artificial intelligence (AI) technology, the realm of medicine is experiencing a paradigm shift, engendering a multitude of prospects and trials for healthcare practitioners, encompassing those devoted to the practice of traditional Chinese medicine (TCM). This study explores the evolving landscape for TCM practitioners in the AI era, emphasizing that while AI can be helpful, it cannot replace the role of TCM practitioners. It is paramount to underscore the intrinsic worth of human expertise, accentuating that artificial intelligence (AI) is merely an instrument. On the one hand, AI-enabled tools like intelligent symptom checkers, diagnostic assistance systems, and personalized treatment plans can augment TCM practitioners' expertise and capacity, improving diagnosis accuracy and treatment efficacy. AI-empowered collaborations between Western medicine and TCM can strengthen holistic care. On the other hand, AI may disrupt conventional TCM workflow and doctor-patient relationships. Maintaining the humanistic spirit of TCM while embracing AI requires upholding professional ethics and establishing appropriate regulations. To leverage AI while retaining the essence of TCM, practitioners need to hone holistic analytical skills and see AI as complementary. By highlighting promising applications and potential risks of AI in TCM, this study provides strategic insights for stakeholders to promote the integrated development of AI and TCM for better patient outcomes. With proper implementation, AI can become a valuable assistant for TCM practitioners to elevate healthcare quality.

Acupuncture and related therapies for atopic eczema: A protocol for systematic review and network meta-analysis.

BACKGROUND: Atopic eczema (AE) is a chronic relapsing dermatological disease characterized by pruritus, dryness, erythema, and lichenification. Acupuncture as an alternative treatment can relieve symptoms, reduce the recurrence, and improve the quality of life (QoL) with less adverse reactions in treating AE. This network meta-analysis (NMA) will comprehensively access the efficacy and safety of different acupuncture therapies for patients with AE, and rank the different acupuncture therapies, in order to present evidence-based medicine evidence for clinical application extensively. METHOD AND ANALYSIS: This study will search 8 electronic databases from the establishment of the database to August 30th, 2022. The screening of literature, data extraction, and risk of bias assessment will be conducted by 2 researchers, respectively. The quality of evidence will be judged by the Grading of Recommendations Assessment, Development and Evaluation system. This NMA will be analyzed with Stata Version. 14.0 and WinBUGS Version.1.4.3. RESULTS: This study will comprehensively access the efficacy and safety of different acupuncture therapies for patients with AE on the severity, itch intensity, emotional symptoms, QoL, and recurrence rate. Moreover, it will further identify which acupuncture therapy is the most effective. CONCLUSION: The findings of this NMA may help patients and therapists choose the best acupuncture therapy in treating AE and furnish reliable evidence for guidelines. REGISTRATION NUMBER: PROSPERO CRD42020203437.

The Effect of Thunder-Fire Moxibustion on Lumbar Disc Herniation: Study Protocol for a Randomized Controlled Trial.

Background: Lumbar disc herniation (LDH) is a common disease seen in orthopedics; it is caused by nucleus pulposus herniation. Its clinical manifestations are low back pain, radiating pain of the lower limbs, and cauda equina symptoms that seriously affect patients' quality of life. At present, oral analgesics are commonly used in the treatment of LDH; but they can produce gastrointestinal reactions and other side effects. Thunder-fire moxibustion is a method that is widely used in China to treat pain syndromes. This study aimed to design a randomized controlled trial to explore the effectiveness and safety of thunder-fire moxibustion in the treatment of lumbar disc herniation. Methods: Ninety patients will be enrolled and randomly divided into one of two groups: the thunder-fire moxibustion group and the acetaminophen group. The thunder-fire moxibustion group will be treated with moxa sticks at BL25, GV3, BL23, and GV4; and after 15 min of local whirling moxibustion, the contralateral acupoints will be treated with moxibustion for 15 min. The study period will include two 10-day courses of treatment, for a total study duration of 20 days. The acetaminophen group participants will take one acetaminophen sustained-release tablet twice a day for the duration of the study period. In contrast, the thunder-fire moxibustion group participants will be treated with thunder-fire moxibustion every other day for 30 min. The primary outcome will be the Japanese Orthopedic Association (JOA) score. Visual analog scale (VAS) and Oswestry Disability Index (ODI) will be used as the secondary outcome measures. Adverse events (AEs) will also be recorded. Assessments will be conducted at baseline, the end of the first and second courses of treatment. Discussion: This study will determine whether thunder-fire moxibustion is more effective and safer than acetaminophen in the treatment of patients with LDH. Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR2000036079.

[Discussion on the essential thought of Ma's warm moxibustion technique for "unblocking fu-organs"].

"Unblocking fu organs" is one of the essential principles of Ma's warm moxibustion technique, characterized as "dredging" and "harmonizing" for either deficiency or excess condition. Under the guidance of this therapeutic thought, the acupoints for moxibustion are mainly selected from the middle and lower parts of the body. Regarding the therapeutic approach, the acupoint prescription for moxibustion should be formed in line with warming and promoting circulation of fu organs; the moxibustion degree should be specially considered, in which, the mild moxibustion is recommended to induce promoting action; and the systematic moxibustion technique should be the root for dredging fu organs and regulating zang organs. Ma's mild moxibustion technique stresses on removing the obstruction of fu organs and emphasizes promoting the qi activity of sanjiao (triple energizer) and regulating the balance of five zang organs.

Efficacy of acupuncture in improving symptoms and quality of life of patients with acne vulgaris: a randomized sham acupuncture-controlled trial.

OBJECTIVE: The aim of this study was to examine the effectiveness of acupuncture in treating the symptoms and quality of life (QoL) of patients with moderate or severe acne vulgaris (AV). METHODS: Participants were randomly assigned (1:1) to receive 12 treatment sessions of acupuncture or sham acupuncture over 4 weeks with 24 weeks of follow-up. The primary outcome was the change from baseline in the Skindex-16 scale total score at treatment completion. Secondary outcomes included Skindex-16 subscale score, Dermatology Life Quality Index scale total score, total lesion count and inflammatory lesion count, and visual analogue scale scores for itch and pain evaluation. RESULTS: There was no statistically significant between-group difference for the primary outcome or any secondary outcomes after 4 weeks of treatment and at 16 and 28 weeks of follow-up, except for the Skindex-16 emotions subscale at week 4 (p = 0.026). No serious adverse events occurred in either group. CONCLUSION: Acupuncture may not effectively relieve the symptoms of patients with moderate or severe AV, or improve QoL. Given the limitations of a relatively short treatment course compared to other studies and the likelihood that sham acupuncture is not inert, further studies with treatment durations of 12 weeks or longer and a waitlist (no treatment) control or Western medicine-treated control group should be considered to evaluate the effects of acupuncture on AV. TRIAL REGISTRATION NUMBER: ChiCTR-1900023649 (Chinese Clinical Trial Registry).

[Effect of transcutaneous auricular vagus nerve stimulation on hyperglycemia and insulin receptors expression in impaired glucose tolerance rats].

OBJECTIVE: To explore the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on blood glucose regulation and the expression of insulin receptors (INR) of hypothalamus, liver and skeletal muscle tissues in impaired glucose tolerance (IGT) rats, so as to reveal its mechanisms underlying improvement of IGT. METHODS: Thirty-six male Wistar rats were randomly divided into control, model, transcutaneous auricular none-vagus nerve stimulation (tnVNS), and taVNS groups (n=9 in each group). The IGT model was established by feeding the rats with high-fat and high-sugar diet for 5 weeks, and subsequent intraperitoneal injection of a dose of streptozotocin (20 mg/kg). Transcutaneous electrostimulation (2 mA, 2 Hz/15 Hz) was applied to auricular concha (taVNS) or auricular margin (tnVNS), respectively. The treatment was conducted for 30 min once daily for 4 weeks. The body weight, fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG) were recorded every week. The contents of plasma insulin (INS), glucagon (GC), glycosylated hemoglobin (GHbA1c) were detected by using enzyme linked immunosorbent assay (ELISA). The expression levels of INR in hypothalamus, liver and skeletal muscle tissues were detected by Western blot. RESULTS: After modeling, the rats' body weight, the contents of FPG, 2 h PG, GC and GHbA1c were significantly up-regulated (P<0.001, P<0.05, P<0.01), and the content of INS and expression of INR in hypothalamus, liver and skeletal muscle tissues were significantly down-regulated in the model group compared with the control group (P<0.001, P<0.01, P<0.05). Following the treatment, the increased FPG, 2 h PG, GC, and the decreased INS and INR expression of hypothalamus, liver and skeletal muscle tissues were apparently reversed in the taVNS group relevant to the model group (P<0.001, P<0.01, P<0.05). Compared with the tnVNS group, the FPG and 2 h PG contents were considerable decreased, and the content of INS and INR expression of hypothalamus and liver were obviously increased in the taVNS group (P<0.001, P<0.05, P<0.01). CONCLUSION: taVNS can improve the blood glucose and insulin sensitivity in IGT rats, which may contribute to its effectiveness in up-regulating the expression of INR in hypothalamus, liver and skeletal muscle tissues.

[Research status and development strategies of moxibustion standardization].

Based on the analysis of the present situation of standardization of moxibustion, it is found that the published standards of acupuncture and moxibustion are predominated at acupoint standard and acupuncture manipulation standard. Moxibusiton standardization mainly focuses on the manipulation. It is relatively lack of the standards of moxibustion materials and device. Four suggestions are put forward on the development strategies of moxibustion standardization: 1. Rectify the current situation that more attention paid to acupuncture rather than moxibustion, strengthen the inheritance of traditional experiences and the excavation of ancient literature, expand the indications of moxibustion and confirm the clinical effect of it. 2. Promote the whole process of moxibustion standardization, starting from moxibustion technique to its material, device and manipulation. 3. Enhance the equipment construction of moxibustion, combine with other build engineering disciplines, e.g. artificial intelligence and communication technology, and construct a multi-disciplinary intersection system. 4. Improve the promotion and development mode of moxibustion, propel all-round development of moxibustion in the clinical application, promotion mode and standardization construction, etc.

[Modulation effect of Acanthopanax senticosus polysaccharides through inflammatory cytokines in protecting immunological liver-injured mice].

The aim of this paper was to discuss the protective effect and mechanism of Acanthopanax senticosus polysaccharides( ASPs) on immunological liver injury caused by conanavalin A( Con A). BALB/c mice were randomly divided into seven groups: control group,model group( Con A),low-,medium-,and high-dose( 36. 25,72. 5,145 mg·kg~(-1)) ASPs groups,bifendate( 200 mg·kg~(-1),positive drug) group and pyrrolidinedithiocarbamate( PDTC,NF-κB inhibitor,200 mg·kg~(-1)) group. ASPs groups and bifendate group were given with corresponding drugs by ig administration once daily for 7 d. Control group,model group and PDTC group were given with normal saline by ig administration once daily for 7 d. After the last ig administration,PDTC was given in DTC group by iv administration( 200 mg·kg~(-1)); 0. 5 h after that,Con A( 20 mg·kg~(-1)) was injected via the tail vein to induce immunological liver injury in all the mice except normal control group. The mice were killed 8 h later and their liver tissues were collected for histopathological examination. The contents of nitric oxide( NO),superoxide dismutase( SOD),malondialdehyde( MDA),reduced glutathione( GSHPX),interleukin( IL-1ß) and tumor necrosis factor( TNF-α) in liver tissues were detected by kit assay. Western blot method was used to detect TNF-α,intercellular cell adhesion molecule-1( ICAM-1),inducible nitric oxide synthase( i NOS) and nuclear factor( NF-κB) protein expression in liver tissues. As compared with model group,ASPs not only could reduce the activity of MDA,NO,IL-1ß and TNF-α,but also increase the content of GSH-PX and SOD; at the same time,the protein expression levels of TNF-α,ICAM-1,i NOS and NF-κB were reduced in liver tissues; in addition,inflammatory cell infiltration was alleviated,hepatocyte cytoplasm was loose and swollen,and nuclear condensation and staining were improved. ASPs has a protective effect on immunological liver injury,and the mechanism may be associated with regulating secretion of inflammatory cytokines and the expression of adhesion factor through NF-κB signaling pathway.

[Progress of Research on Mechanism of Acupuncture for Diabetes Mellitus].

Acupuncture has been used to treat diabetes mellitus (DM) for more than one thousand years. In the present paper, we review new progress of researches on the underlying mechanism of acupuncture intervention for DM. Results showed that acupuncture intervention can relieve DM by 1) reducing body weight through up-regulating leptin level, suppressing insulin resistance and appetite to reduce food intake possibly by way of down-regulating expression of neuropeptide Y in the hypothalamus, retarding gastric emptying velocity, increasing small intestinal peristalsis, raising plasma levels of glucagon-like peptide-1 (GLP-1) and peptide YY, etc.; 2) improving pancreas function, raising insulin sensitivity to improve insulin resistance possibly by activating AMP-activated protein kinase and sirtuin 1/ peroxisome proliferator-activated receptor γ coactivator 1 α signaling, up-regulating activities of cholinergic nerve activity and nitric oxide synthase, and inhibiting apoptosis of pancreatic beta-cells; 3) lowering blood glucose possibly by increasing anaerobic glucose metabolism, regulating activities of vagal and sympathetic nerves; 4) adjusting the levels of related hormones such as melatonin, insulin, glucocorticold, epinephrine, etc. Moreover, acupuncture treatment combined with hypoglycemic drugs has a synergic effect in lowering blood glucose, suggesting a potentially effective approach for improving DM and being worthy of further studying in clinical practice.

Auricular vagus nerve stimulation enhances central serotonergic function and inhibits diabetic neuropathy development in Zucker fatty rats.

Painful neuropathy is a frequent comorbidity in diabetes. Zucker diabetic fatty (fa/fa) rats develop type 2 diabetes spontaneously with aging and show nociceptive hypersensitivity at the age of 13 weeks. In preclinical and clinical studies, the treatment of diabetic neuropathy is challenging, but complementary medicine such as transcutaneous auricular vagus nerve stimulation (taVNS) appears beneficial to the relief of neuropathic pain. However, the mechanism behind the effectiveness of taVNS remains unclear. In this study, we show that daily 30-min taVNS (2/15 Hz, 2 mA) for consecutive 27 days effectively inhibited the development of nociceptive hypersensitivity in Zucker diabetic fatty rats as detected by thermal hyperalgesia and mechanical allodynia in hindpaw. We also demonstrated that this beneficial effect in nociceptive behavior is related to an elevated serotonin (5-HT) plasma concentration and an upregulated expression of 5-HT receptor type 1A (5-HT1AR) in hypothalamus. We conclude that daily 30-min taVNS sessions lessen diabetic neuropathy development by enhancing serotonergic function in genetically diabetes prone individuals. Perspective This article presents taVNS as a new approach to inhibit the development of diabetic neuropathy in genetically prone individuals. This approach could potentially help clinicians who seek to avoid the complication of neuropathic pain in diabetic patient or to relieve the pain if there was one.

[Protective effect of Dendrobium candidum on isoproterenol induced cardiac hypertrophy in rats].

To study the effect and mechanism of Dendrobium candidum on isoproterenol-induced myocardial hypertrophy in rats, 60 healthy SD rats(30 males and 30 females) were randomly divided into 5 groups(12 in each group): normal group, model group, three D. candidum preventive administration groups(0.09, 0.18, 1.1 g·kg⁻¹). Except for the normal group, rats of other groups were injected back subcutaneously with ISO(5 mg·kg⁻¹) for 10 consecutive days. At the same time, preventive administration groups began to give different doses of the sample for 30 days and model group began to give normal saline. Left ventricular systolic pressure(LVSP) was measured in each group by common carotid artery cannulation, and the left ventricle(LW)/tibia length, heart weight index(HWI) and myocardial hydroxyproline(Hydro) content were calculated. Myocardial tissue HE staining and Masson staining were used to observe the myocardial structure and the degree of myocardial fibrosis respectively. Atrial natriuretic peptide(ANP), brain natriuretic peptide(BNP), and cardiac troponin I(cTN-I) concentration were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that as compared with the normal group, the levels of ANP, BNP and cTN-I in plasma were significantly increased in ISO-induced hypertrophic rats; as compared with the model group, D. candidumcan inhibit ISO-induced ventricular pressure and ventricular hypertrophy, reduce myocardial collagen synthesis, improve myocardial fibrosis and ventricular remodeling, and significantly down-regulate ANP, BNP and cTN-I levels in plasma. This study shows that D. candidum has a protective effect on isoproterenol-induced cardiac hypertrophy.

[Acupuncture combined with oral western medication for Meniere's disease: a randomized controlled trial].

OBJECTIVE: To compare the effect difference between acupuncture combined with western medication and simple western medication for Meniere's disease. METHODS: Ninety-six patients with Meniere's disease were randomly assigned into a combination group (48 cases, 12 cases dropping) and a medication group (48 cases, 9 cases dropping). Betastatin mesylate tablets (once 12 mg, 3 times a day) and mecobalamin tablets (once 0.5 mg, 3 times a day) were prescribed orally in the two groups. Acupuncture was used in the combination group, twice a week, 20 min a time, and the acupoints were Baihui (GV 20), Fengchi (GB 20), Tinggong (SI 19), Hegu (LI 4), Quchi (LI 11), Zusanli (ST 36), Fenglong (ST 40), Taichong (LR 3), Taixi (KI 3) and Tianshu (ST 25). All the treatment was given for continuous 12 weeks. The symptoms were observed by dizziness handicap inventory (DHI), tinnitus handicap inventory (THI), pure tone audiometry score and stuffy ear visual analogue scale (VAS). The effects were compared in the aspects of dizziness, hearing and activity. RESULTS: The scores of DHI, THI, pure tone audiometry and VAS scores after treatment were lower than those before treatment in the two groups (all P<0.05), with lower scores of the above 4 indexes in the combination group after treatment (all P<0.05). The difference values before and after treatment of the 4 indexes in the combination group were higher than those in the medication group (all P<0.05). The effective rates of dizziness, hearing and activity in the combination group were 97.2% (35/36), 91.7% (33/36), 88.9% (32/36), which were better than 71.8% (28/39), 74.4% (29/39) and 69.2% (27/39) in the medication group (all P<0.05). CONCLUSION: Acupuncture combined with conventional medication achieve better effect than simple conventional medication.

(R)-panaxadiol by whole cells of filamentous fungus Absidia coerulea AS 3.3382.

The microbial transformation of 20(R)-panaxadiol (PD) by the fungus Absidia coerulea AS 3.3382 afforded three new and three known metabolites. The structures of the metabolites were characterized as 3-oxo-20(R)-panaxadiol (1), 3-oxo-7ß- hydroxyl-20(R)-panaxadiol (2), 3-oxo-22ß-hydroxyl-20(R)-panaxadiol (3), 3-oxo- 7ß,22ß-dihydroxyl-20(R)-panaxadiol (4), 3-oxo-7ß,24ß-dihydroxyl-20(R)-panaxadiol (5), and 3-oxo-7ß,24α-dihydroxyl-20(R)-panaxadiol (6). Among them, 2-4 were new compounds. In addition, compounds 3 and 4 exhibited significant anti-hepatic fibrosis activity.

Effect of electroacupuncture on thermal pain threshold and expression of calcitonin-gene related peptide, substance P and γ-aminobutyric acid in the cervical dorsal root ganglion of rats with incisional neck pain.

OBJECTIVE: Acupuncture therapy effectively reduces post-surgical pain, but its mechanism of action remains unclear. The aim of this study was to investigate whether expression of γ-aminobutyric acid (GABA) and the neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) in the primary sensory neurons of cervical dorsal root ganglia (DRG) are involved in electroacupuncture (EA)-induced analgesia in a rat model of incisional neck pain. METHODS: The pain model was established by making a longitudinal midline neck incision in 60 rats. Another 15 rats underwent sham surgery (normal group). Post-incision, 15 rats remained untreated (model group) and 45 rats underwent EA (frequency 2/100 Hz, intensity 1 mA) at bilateral LI18, LI4-PC6 or ST36-GB34 (n=15 each) for 30 min at 4 hours, 24 hours, and 48 hours post-surgery, followed by thermal pain threshold (PT) measurement. 30 min later, the rats were euthanased and cervical (C3-6) DRGs removed for measurement of immunoreactivity and mRNA expression of SP/CGRP and the GABAergic neuronal marker glutamic acid decarboxylase 67 (GAD67). RESULTS: Thermal PT was significantly lower in the model group versus the normal group and increased in the LI18 and LI4-PC6 groups but not the ST36-GB34 group compared with the model group. Additionally, EA at LI18 and LI4-PC6 markedly suppressed neck incision-induced upregulation of mRNA/protein expression of SP/CGRP, and upregulated mRNA/protein expression of GAD67 in the DRGs of C3-6 segments. CONCLUSIONS: EA at LI18/LI4-PC6 increases PT in rats with incisional neck pain, which is likely related to downregulation of pronociceptive mediators SP/CGRP and upregulation of the inhibitory transmitter GABA in the primary sensory neurons of cervical DRGs.

Auricular acupuncture and biomedical research--A promising Sino-Austrian research cooperation.

Treatment by auricular acupuncture has a long history. Ear-acupoint research has been advancing step by step in China and also in Europe. Auricles are rich in nerves, therefore a close relationship with different functions of the human body has been proved by the research teams of the two main authors of this article from China and Austria. In recent years, great progress has been made in the research of regulating human body functions through electroacupuncture at the auricular branch of the vagus nerve, which is part of auricular acupuncture therapy. It is well known that the auricular branch of the vagus nerve is the only peripheral pathway to the cerebral cortex. Studies of the Chinese team on hypertension, diabetes, epilepsy and depression have shown that the mechanism of auricular vagus nerve stimulation (VNS) may be comparable with cervical VNS in terms of pathways. Auricular VNS has a broad clinical application prospect.

Transcutaneous vagus nerve stimulation induces tidal melatonin secretion and has an antidiabetic effect in Zucker fatty rats.

Melatonin plays a protective role in type 2 diabetes (T2D) through regulation of glucose metabolism. Whether transcutaneous vagus nerve stimulation (taVNS) is antidiabetic and whether a modulated melatonin production is involved in the antidiabetic mechanism of taVNS is unknown. In this study, once daily 30 min noninvasive taVNS was administered in Zucker diabetic fatty (ZDF, fa/fa) and Zucker lean (ZL, +/fa) littermates under anesthesia for 5 consecutive weeks. The acute and chronic influences of taVNS on the secretion of melatonin were studied as well as the effects of taVNS on blood glucose metabolism. We found that naïve ZDF rats develop hyperglycemia naturally with age. Each taVNS session would trigger a tidal secretion of melatonin both during and after the taVNS procedure and induce an acute two-phase glycemic change, a steep increase followed by a gradual decrease. Once daily taVNS sessions eventually reduced the glucose concentration to a normal level in seven days and effectively maintained the normal glycemic and plasma glycosylated hemoglobin (HbAlc) levels when applied for five consecutive weeks. These beneficial effects of taVNS also exist in pinealectomized rats, which otherwise would show overt and continuous hyperglycemia, hyperinsulinemia, and high HbAlc levels. We concluded that multiple taVNS sessions are antidiabetic in T2D through triggering of tidal secretion of melatonin. This finding may have potential importance in developing new approaches to the treatment of T2D, which is highly prevalent, incurable with any current approaches, and very costly to the world.