Brain Activities Responding to Acupuncture at ST36 (zusanli) in Healthy Subjects: A Systematic Review and Meta-Analysis of Task-Based fMRI Studies.

Purpose: Stomach 36 (ST36, zusanli) is one of the important acupoints in acupuncture. Despite clinical functional magnetic resonance imaging (fMRI) studies of ST36 acupuncture, the brain activities and the neural mechanism following acupuncture at ST36 remain unclear. Methods: Literature searches were conducted on online databases, including MEDLINE, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, WeiPu database, and China Biology Medicine, for task-based fMRI studies of acupuncture at ST36 in healthy subjects. Brain regions activated by ST36 acupuncture were systematically evaluated and subjected to seed-based d mapping meta-analysis. Subgroup analysis was conducted on control procedures, manual acupuncture, electrical acupuncture (EA), and acupuncture-specific activations. Meta-regression analysis was performed to explore the effects of needle retention time on brain activities following ST36 acupuncture stimulation. The activated brain regions were further decoded and mapped on large-scale functional networks to further decipher the clinical relevance of acupuncturing at ST36. Results: A total of sixteen studies, involving a total of 401 right-handed healthy participants, that satisfied the inclusion criteria were included in the present meta-analysis. Meta-analysis showed that acupuncturing on ST36 positively activates the opercular part of the right inferior frontal gyrus (IFG.R), left superior temporal gyrus (STG.L), and right median cingulate/paracingulate gyri (MCG.R) regions. Needle retention time in an acupuncture session positively correlates with the activation of the left olfactory cortex, as shown in meta-regression analysis. Subgroup analysis revealed that EA stimulation may be a source of heterogeneity in the pooled results. Functional network mappings showed that the activated areas were mapped to the auditory network and salience network. Further functional decoding analysis showed that acupuncture on ST36 was associated with pain, secondary somatosensory, sound and language processing, and mood regulation. Conclusion: Acupuncture at ST36 in healthy individuals positively activates the opercular part of IFG.R, STG.L, and MCG.R. The left olfactory cortex may exhibit positive needle retention time-dependent activities. Our findings may have clinical implications for acupuncture in analgesia, language processing, and mood disorders. Systematic Review Registration: https://inplasy.com/inplasy-2021-12-0035.

Compound Chaijin Jieyu Tablets ameliorating insomnia complicated with depression by improving synaptic plasticity via regulating orexin A, melatonin, and acetylcholine contents / 数字中医药（英文）

@#Objective To investigate the efficacy and mechanism of action of Compound Chaijin Jieyu Tablets (复方柴金解郁片, CCJJYT) in rats with insomnia complicated with depression. Methods Seventy-two Sprague-Dawley rats were randomly assigned into eight groups: the control, chronic unpredictable mild stress (CUMS), sleep deprivation (SD), CUMS + SD, positive drug (venlafaxine hydrochloride + diazepam), CCJJYT high-dose (CCJJYT˗2×), medium-dose (CCJJYT˗1×), and low-dose (CCJJYT˗0.5×) groups, with nine rats in each group. Depression-like behavior was evaluated by body weight, food intake, and behavioral tests such as the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST), and pentobarbital-induced sleep test (PST). Hematoxylin-eosin (HE) staining and Golgi-Cox staining were used to observe changes in pathological tissue and synaptic morphology, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of orexin-A and acetylcholine. The expression levels of orexin receptor 1 (OXR1), melatonin receptor 1 (MT1A), melatonin receptor 2 (MT1B), acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) were detected by immunohistochemistry and Western blot. Results In the present study, rats in the model group showed significant behavioral changes as well as a reduction in hippocampal dendritic branch length and synaptic number, along with increasing the content of orexin A and acetylcholine (P< 0.05), and altered expression levels of OX1R, MT1A, MT1B, ChAT, and AChE in the hippocampus and prefrontal cortex after modeling (P < 0.05). CCJJYT can improve depressive insomnia behavior and synaptic plasticity of rats (P < 0.05), which is similar to that of the positive drug group. It can also decrease the content of orexin A and acetylcholine, and reduce the expression levels of OXR1 and ChAT in hippocampus and prefrontal cortex (P < 0.05), and increase the expression levels of MT1A, MT1B, and AChE proteins (P < 0.05). Conclusion CCJJYT has good antidepressant and insomnia effects, probably through the regu-lation of orexin-A, melatonin, and acetylcholine content in hippocampus and prefrontal cortex of rats, improving synaptic plasticity and thus exerting antidepressant and insomnia effects.

Autophagy is involved in the neuroprotective effect of nicotiflorin.

ETHNOPHARMACOLOGICAL RELEVANCE: Nicotiflorin is a flavonoid glycoside derived from the traditional Chinese medicine FlosCarthami, dried petals of Carthamus tinctorius L., and has been confirmed to be a promising novel drug candidate for ischemic stroke. Yet, the exact role of nicotiflorin in cerebral I/R injury is uncharacterized and the possible mechanisms have not been clearly expounded. AIM OF THE STUDY: The present study was designed to determine the effect of nicotiflorin on cerebral ischemia/reperfusion (I/R) injury and its relationship with autophagy. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) in rats and oxygen-glucose deprivation and reintroduction (OGD/R) in SH-SY5Y cells were established in in vivo and in vitro models, respectively. The severity of MCAO was assessed by brain infarct size, neurological scores and survival rate. The severity of OGD/R was evaluated by cell viability, lactate dehydrogenase (LDH) release and cell apoptosis. The level of autophagy was evaluated both in vivo and in vitro. Autophagosomes were observed using transmission electron microscopy and autophagic flux was measured using mRFP-GFP-tandem fluorescent LC3 adenovirus. Autophagy-related proteins (LC3-II/I, SQSTM1, beclin-1, Phospho-mTOR/mTOR) were measured by immunoblot. Autophagy-related mRNA levels (Becn1, Atg7) were detected by Real-Time PCR. Inhibition of autophagy was implemented by 3-Methyladenine (3-MA) or chloroquine in vitro. RESULTS: In vivo, nicotiflorin treatment alleviated brain damage and neurological deficit while it dramatically increased 72 h survival rate in rats. In vitro, nicotiflorin treatment also ameliorated the severity of OGD/R. Moreover, nicotiflorin treatment increased ischemic penumbra autophagy (autophagosomes, BECN1, LC3-II/I ratio, SQSTM1, Phospho-mTOR/mTOR, Atg7). In vitro, nicotiflorin likewise enhanced autophagy and promoted autophagy flux. Furthermore, the blockade of autophagy by 3-MA or chloroquine disabled the efficacic of nicotiflorin in preventing cell damage upon OGD/R insult. CONCLUSION: These findings suggest that autophagy plays a significant role in the protective effect of nicotiflorin against ischemic stroke.

Crataegus pinnatifida polysaccharide alleviates colitis via modulation of gut microbiota and SCFAs metabolism.

Inflammatory bowel disease (IBD) afflicted individual and most medications have side-effects. Crataegus pinnatifida (Hawthorn), which is a safe medicine and food homolog plant, has been reported to prevent colitis in murine. Yet the bioactivity component and the underlying molecular mechanism remain unclear. Here, we established a direct link between colitis induced by dextran sulphate sodium (DSS) in mice and polysaccharide HAW1-2 isolated from hawthorn. Our results showed HAW1-2 restored the pathological lesions in colon and inhibited the expression of inflammatory cytokines including IL-1ß, IL-6 and TNF-α. Meanwhile, IKKα/ß, IκBα, NF-κB and the phosphorylation levels were inhibited significantly. These findings suggested HAW1-2 could alleviate the inflammation of colon. Further, we found the composition of gut microbiota was modified and Bacteroides including Alistipes and Odoribacter were significantly enriched. Besides, we showed Alistipes and Odoribacter were positively co-related with acetic acid and propionic acid while were negatively co-related with inflammatory cytokines. Finally, we demonstrated the anti-inflammation activity of HAW1-2 might be induced by acetic acid. Together, the present data revealed HAW1-2 could directly modify the gut microbiota, especially for Bacteroides, and generate SCFAs to inhibit colitis. It also implies microbiota-directed intervention in IBD patients should be particularly given more attention.

Intestinal microbes derived butyrate is related to the immunomodulatory activities of Dendrobium officinale polysaccharide.

Although immunomodulatory activities of Dendrobium officinale polysaccharide has been investigated for many years, yet the potential contribution of its metabolite derived from intestinal microbes on immunoregulation effect has not been reported. In this study, polysaccharide DOW-5B with average molecular weight of 39.4 kDa was isolated from the stem of Dendrobium officinale Kimura et Migo. The carbohydrate content was 91.97% and no protein was detected. The monosaccharide analysis showed this polysaccharide was composed of glucuronic acid and glucose at a molar ratio (M/G) of 1.2:19.4. Animal test indicated DOW-5B increased the diversity of gut microbiota on mice. Beneficial microbes such as Ruminococcus, Eubacterium, Clostridium, Bifidobacterium, Parabacteroides and Akkermansiamuciniphila increased while harmful bacteria in Proteobacteria decreased. Surprisingly, DOW-5B promoted gut microbes to generate more butyrate and mainly produced by Parabacteroides_sp_HGS0025. Further, we found the health of large intestine as well as immunity response of mice was improved. In addition, Parabacteroides_sp_HGS0025 positively correlated with butyrate, IgM, IL-10, and TNF-α products in intestine and mice blood, respectively. The data suggested that Dendrobium officinale polysaccharide has function on immunity may be mediated by butyrate. It adds new evidence to support the basis of how herbal polysaccharides affect immunity.

Celosins inhibit atherosclerosis in ApoE-/- mice and promote autophagy flow.

ETHNOPHARMACOLOGICAL RELEVANCE: Semen celosiae is a traditional Chinese medicine for purging hepatic pathogenic fire and removing nebula to improve eyesight, treating hepatopyretic vertigo and hypertension. It possesses a serial of potential bioactivities such as hepatoprotection, anti-tumor and anti-inflammatory, anti-diabetes. The triterpenoid saponins celosins from it were proved to have hepatoprotection, lipid lowing and anti-inflammatory. However, the anti-atherosclerosis activities were not reported to date. AIM OF THE STUDY: This study was designed to examine the therapeutic effects of celosins (CES), the active constituents extracted from Semen celosiae. MATERIALS AND METHODS: Atherosclerosis model by feeding high fat diet for 12 weeks in ApoE-/- mice and foam cell model by ox-LDL-treated peritoneal macrophages were performed. The lipid plaque was measured by histopathological analysis. The LC3 dots in the aortic root lesion examined through tissue immunofluorescence. The peritoneal macrophage phagocytosis, formation of foam cells, genes associated protein expression and autophagy flux were measured on foam cell model by oxidized low-density lipoprotein (Ox-LDL) stimulating peritoneal macrophages. The mRNA expression of CD36, SR-A1, ABCA1 and ABCG1 were determined by Real-Time PCR method. The expressions of LC3 and beclin 1 were measured using Western blot. RESULTS: CES (10, 30, 90mg/kg; p.o.) administrated for 4 weeks significantly reduced the prevalence of the relative area of plaque in mouse aorta, and showed the therapeutic effect on atherosclerosis. In the tissue section of immunofluorescence for aortic root, compared with high fat diet model group, the number of autophagy bodies in CES group increased significantly, suggesting that inhibiting atherosclerosis effect of CES may be related to its promoting autophagy. In vitro, CES significantly reduced phagocytosis of macrophages on lipid and formation rate of foam cells. CES down-regulated the mRNA expression of CD36 and SR-A1 while up-regulated mRNA expression of ABCA1 and ABCG1. Further, CES increased the autophagy specific protein LC3 and beclin 1, and it also increased the level of autophagy in the cells, and promoted the process of autophagy. CONCLUSIONS: The therapeutic effect of CES on atherosclerosis may be related to the promotion of autophagy.