Remodelling the inguinal adipose sensory system to switch on the furnace: Electroacupuncture stimulation induces brown adipose thermogenesis.

Brown and white adipose tissue mediate thermogenesis through the thermogenetic centre of the brain, but safe methods for activating thermogensis and knowledge of the associated molecular mechanisms are lacking. We investigated body surface electroacupuncture stimulation (ES) at ST25 (targeted at the abdomen) induction of brown adipose thermogenesis and the neural mechanism of this process. Inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) were collected and the thermogenic protein expression levels were measured to evaluate iBAT thermogenesis capacity. The thermogenic centre activating region and sympathetic outflow were evaluated based on neural electrical activity and c-fos expression levels. iWAT sensory axon plasticity was analysed with whole-mount adipose tissue imaging. ES activated the sympathetic nerves in iBAT and the c-fos-positive cells induced sympathetic outflow activation to the iBAT from the medial preoptic area (MPA), the dorsomedial hypothalamus (DM) and the raphe pallidus nucleus (RPA). iWAT denervation mice exhibited decreased c-fos-positive cells in the DM and RPA, and lower recombinant uncoupling orotein 1 peroxisome proliferator-activated receptor, ß3-adrenergic receptor, and tyrosine hydroxylase expression. Remodelling the iWAT sensory axons recovered the signal from the MPA to the RPA and induced iBAT thermogenesis. The sympathetic denervation attenuated sensory nerve density. ES induced sympathetic outflow from the thermogenetic centres to iBAT, which mediated thermogenesis. iWAT sensory axon remodelling induced the MPA-DM-RPA-iBAT thermogenesis pathway.

Electroacupuncture stimulation ameliorates cognitive impairment induced by long-term high-fat diet by regulating microglial BDNF.

Long-term high-fat diet (HFD) in adolescents leads to impaired hippocampal function and increases the risk of cognitive impairment. Studies have shown that HFD activates hippocampal microglia and induces hippocampal inflammation, which is an important factor for cognitive impairment. Electroacupuncture stimulation (ES), a nerve stimulation therapy, is anti-inflammatory. This study explored its therapeutic potential and mechanism of action in obesity-related cognitive impairment. 4-week-old C57 mice were given either normal or HFD for 22 weeks. At 19 weeks, some of the HFD mice were treated with ES and nigericin sodium salt. The cognitive behavior was assessed through Morris water maze test at 23 weeks. Western blotting was used to detect the expression levels of pro-inflammatory molecules IL-1ß and IL-1R, synaptic plasticity related proteins synaptophysin and Postsynaptic Density-95 (PSD-95), and apoptotic molecules (Caspase-3 and Bcl-2), in the hippocampus. The number, morphology, and status of microglia, along with the brain-derived neurotrophic factor（BDNF） content, were analyzed using immunofluorescence. ES treatment improved cognitive deficits in HFD model mice, and decreased the expressions of microglial activation marker, CD68, and microglial BDNF. Inhibition of proinflammatory cytokine, IL-1ß, and IL-1R promoted PSD-95 and synaptophysin expressions. Peripheral NLRP3 inflammasome agonist injections exacerbated the cognitive deficits in HFD mice and promoted the expressions of IL-1ß and IL-1R in the hippocampus. The microglia showed obvious morphological damage and apoptosis. Collectively, our findings suggest that ES inhibits inflammation, regulates microglial BDNF, and causes remodeling of hippocampal function in mice to counteract obesity-like induced cognitive impairment. Overexcitation of peripheral inflammasome complexes induces hippocampal microglia apoptosis, which hinders the effects of ES.

Herb-symptom analysis of Erchen decoction combined with Xiebai powder formula and its mechanism in the treatment of chronic obstructive pulmonary disease.

Background: In recent years, the incidence and mortality rates of chronic obstructive pulmonary disease (COPD) have increased significantly. Erchen Decoction combined with Xiebai Powder (ECXB) formula is mainly used to treat lung diseases in traditional Chinese medicine (TCM). However, the active ingredients of ECXB formula, COPD treatment-related molecular targets, and the mechanisms are still unclear. To reveal its underlying action of mechanism, network pharmacology, molecular docking, and molecular dynamic (MD) simulation approaches were used to predict the active ingredients and potential targets of ECXB formula in treating COPD. As a result, Herb-Symptom analysis showed that the symptoms treated by both TCM and modern medicine of ECXB formula were similar to the symptoms of COPD. Network pharmacology identified 170 active ingredients with 137 targets, and 7,002 COPD targets was obtained. 120 targets were obtained by intersection mapping, among which the core targets include MAPK8, ESR1, TP53, MAPK3, JUN, RELA, MAPK1, and AKT1. Functional enrichment analysis suggested that ECXB formula might exert its treat COPD pharmacological effects in multiple biological processes, such as cell proliferation, apoptosis, inflammatory response, and synaptic connections, and ECXB formula treated COPD of the KEGG potential pathways might be associated with the TNF signaling pathway, cAMP signaling pathway, and VEGF signaling pathway. Molecular docking showed that ECXB formula treatment COPD core active ingredients can bind well to core targets. MD simulations showed that the RELA-beta-sitosterol complex and ESR1-stigmasterol complex exhibited higher conformational stability and lower interaction energy, further confirming the role of ECXB formula in the treatment of COPD through these core components and core targets. Our study analyzed the medication rule of ECXB formula in the treatment of COPD from a new perspective and found that the symptoms treated by both TCM and modern medicine of ECXB formula were similar to the symptoms of COPD. ECXB formula could treat COPD through multi-component, multi-target, and multi-pathway synergistic effects, providing a scientific basis for further study on the mechanism of ECXB formula treatment of COPD. It also provides new ideas for drug development.

Mushroom-brush transitional conformation of mucus-inert PEG coating improves co-delivery of oral liposome for intestinal metaplasia therapy.

The blocking of gastric mucosal intestinal metaplasia (IM) has been considered to be the pivotal method to control the occurrence of gastric cancer. However, there is still a lack of effective therapeutic agent. Here, we developed mucus-penetrating liposome system by covering surface with polyethylene glycol (PEG) chains (hydrophilic and electroneutral mucus-inert material) to co-delivery candidate drugs combination. Then studied the impact on the transmucus performance of different conformations, which were constructed by controlling the density of PEG chains on the surface. The results showed that the particle size of 5%PEG-Lip was less than 120 nm, the polydispersity index was less than 0.3, and the surface potential tended to be neutral. The D value (long chain spacing) of 5% PEG-Lip was 3.25 nm, which was close to the RF value (diameter of spherical PEG long chain group without external force interference) of 3.44 nm, and the L value (extended length) was slightly larger than 3.44 nm. In this case, PEG showed mushroom-brush transitional conformation on the surface of liposomes. This conformation was not only promoted stable delivery, but also shielded the capture of mucus more favorably, leading to a more unrestricted transportation in mucus. The further in vivo experimental results demonstrated the rapid distribution of liposomes, which gradually appeared both in the superficial and deep glandular of mucosa and gland cells at 1 h and absorbed into the cell cytoplasm at 6 h. The 5% PEG-Lip with the mushroom-brush transitional configuration recalled abnormal organ index and improved inflammation and intestinal metaplasia. The modified PEG conformation assay presented here was more suitable for liposomes. This PEG-modified liposome system has potential of mucus-penetrating and provides a strategy for local treatment of gastric mucosal intestinal metaplasia.

[Mechanism and protocol optimization of acupuncture in treatment of obesity based on sympathetic nerve system].

The physiological function of adipose tissue is dominated by the sympathetic nerve system (SNS), but obesity and other diseases may cause the abnormality of the SNS signaling pathway. Acupuncture has been proved to be an effective the-rapy to improve the function of SNS in adipose tissue. Based on the physiological and pathological significance of SNS, this paper reviewed the molecular pathways in which acupuncture directly or indirectly regulated the function of SNS in adipose tissue. As the mechanism of electroacupuncture in regulating autonomic nerves was continuously illuminated, the adjustment of acupuncture mode, such as selection of acupoints in different nerve segments and adjustment of stimulation parameters of electroacupuncture, presumedly induced different content ratios of neurotransmitters released by SNS efferent axons, including noradrenaline and neuropeptide Y, thereby producing different effects on weight loss. Therefore, the specific connections between various acupuncture modes and neurotransmitters released by SNS enriched the intrinsic nerve coding of acupoints, thus optimizing the acupoint selection protocol for the treatment of obesity.

Chitosan-Coated Selenium Nanoparticles Attenuate PRRSV Replication and ROS/JNK-Mediated Apoptosis in vitro.

Introduction: Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication. Methods: In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 µM). Subsequently, the concentrations of hydrogen peroxide (H2O2) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID50, and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot. Results: The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H2O2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi. Conclusion: These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.

Promising traditional Chinese medicine for the treatment of cholestatic liver disease process (cholestasis, hepatitis, liver fibrosis, liver cirrhosis).

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver disease (CLD) is mainly characterized by cholestasis. If not treated, it will deteriorate to cholestatic hepatitis, liver fibrosis, liver cirrhosis, and even liver failure. CLD has a high clinical incidence, and limited treatment with single therapy. In the long-term clinical exploration, traditional Chinese medicine (TCM) has been corroborated with unique therapeutic effects on the CLD process. AIM OF THIS REVIEW: This paper summarizes the effective single and compound TCMs for the treatment of CLD. According to 4 important clinical stages of CLD: cholestasis, hepatitis, liver fibrosis, liver cirrhosis, pharmacological effects and mechanisms of 5 typical TCM examples are reviewed, aims to provide basis for clinical drug selection in different processes of CLD. MATERIALS AND METHODS: Relevant scientific articles regarding therapeutic effects of TCM for the CLD were collected from different databases. We collated three single herbs including Artemisia scoparia Waldst. et Kit. or Artemisia capillaris Thunb. (Artemisiae Scopariae Herba, Yin Chen in Chinese), Paeonia lactiflora Pall. or Paeonia veitchii Lynch. (Paeoniae radix rubra, Chi Shao in Chinese), Poria cocos (Schw.) Wolf (Poria, Fu Ling in Chinese), and two compound herbs of Huang Qi Decoction (HQD) and Yin Chen Hao Decoction (YCHD) to studied and analyzed. RESULTS: We proposed five promising TCMs treatments for the important developmental stages of CLD. Among them, Yin Chen is an essential medicine for protecting liver and gallbladder, and its TCM prescription is also a promising strategy for cholestasis. Based on clinical evidence, high-dose application of Chi Shao is a clinical special treatment of cholestasis hepatitis. Fu Ling can regulate immune cells and increase antibody levels in serum, which is expected to be an emerging therapy to prevent cholestatic liver fibrosis to cirrhosis. HQD can be used as routine clinical medicine for liver fibrosis. In addition, YCHD can exert better comprehensive advantages with multiple components, can treat the whole course of CLD and prevent it from developing to the end-stage. CONCLUSION: Yin Chen, Chi Shao, Fu Ling, HQD and YCHD have shown good clinical efficacy in controlling the development of CLD. Clinically, it is easier to curb the development of CLD by adopting graded diagnosis and treatment measures. We suggest that CLD should be risk stratified in clinical treatment to ensure personalized treatment for patients, so as to slow down the development of the disease.

An effective method for preventing cholestatic liver injury of Aucklandiae Radix and Vladimiriae Radix: Inflammation suppression and regulate the expression of bile acid receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR) were used to treat gastrointestinal, liver and gallbladder diseases at practice. In most conditions, VR was used to be a substitute of AR or a local habit may attribute to the same main active ingredients Costunolide and Dehydrocostus lactone, which presented many similar pharmacological activities. However, other different lactone compounds in AR and VR also play a role in disease treatment, so the difference in therapeutic effects of AR and VR in related diseases needs to be further studied. AIMS OF THE STUDY: Revealing the differences between the chemical compounds of the total lactone extracts of AR and VR (TLE of AR and VR) and the differences in the protective effects of cholestatic liver injury to ensure rational use of AR and VR. STUDY DESIGN AND METHODS: The macroporous adsorption resin was used to purify and enrich the lactone compounds to obtain the total lactone extracts of AR and VR. HPLC-PDA was used to obtain the data to establish chemical fingerprint and chemometric analysis to compare similarities and differences between TLE of AR and VR. The pharmacodynamic experiment revealed how TLE of AR and VR to show protect effects on cholestatic liver injury. RESULTS: Similarity analysis results showed TLE of AR and VR had a high similarity (>0.9). Nevertheless, difference analysis results showed 4 compounds, Costunolide, Dehydrocostus lactone, 3ß-acetoxy-11ß-guaia-4 (15), 10 (14)-diene-12,6α-olide and vladinol F may contribute to the differences between them. The pharmacodynamics experiments results showed the TLE of AR and VR affected the different liver cholate-associated transporters mRNA expression (TLE of AR up-regulated CYP7A1, TLE of VR down-regulated FXR and BSEP), the TLE of AR and VR had an effect to regulate biochemical indicators (AST, ALT, ALP, TBA) of liver function, and TLE of VR was better than TLE of AR in reducing the expression of inflammatory factors (IL-6 and IL-1ß). CONCLUSION: The liver protection of AR and VR have been confirmed, but the differences of material basis and mechanism of drug efficacy needed further study to guarantee formulation research and provide theoretical references for clinical rational applications of AR and VR.

A comprehensive review of ethnopharmacology, phytochemistry, pharmacology, and pharmacokinetics of Schisandra chinensis (Turcz.) Baill. and Schisandra sphenanthera Rehd. et Wils.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (called bei-wuweizi in Chinese, S. chinensis) and Schisandra sphenanthera (called nan-wuweizi in Chinese, S. sphenanthera) are two highly similar plants in the Magnoliaceae family. Their dried ripe fruits are commonly used as traditional Chinese medicine in the treatment of coughs, palpitation, spermatorrhea, and insomnia. They also are traditionally used as tonics in Russia, Japan, and Korea. AIM OF THE REVIEW: S. chinensis and S. sphenanthera are similar in appearance, traditional applications, ingredient compositions, and therapeutic effects. This review, therefore, aims to provide a systematic insight into the botanical background, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicology of S. chinensis and S. sphenanthera, and to explore and present the similarities and differences between S. chinensis and S. sphenanthera. MATERIALS AND METHODS: A comprehensive literature search regarding S. chinensis and S. sphenanthera was collected by using electronic databases including PubMed, SciFinder, Science Direct, Web of Science, CNKI, and the online ethnobotanical database. RESULTS: In the 2020 Edition of Chinese Pharmacopoeia (ChP), there were 100 prescriptions containing S. chinensis, while only 11 contained S. sphenanthera. Totally, 306 and 238 compounds have been isolated and identified from S. chinensis and S. sphenanthera, respectively. Among these compounds, lignans, triterpenoids, essential oils, phenolic acid, flavonoids, phytosterols are the major composition. Through investigation of pharmacological activities, S. chinensis and S. sphenanthera have similar therapeutic effects including hepatoprotection, neuroprotection, cardioprotection, anticancer, antioxidation, anti-inflammation, and hypoglycemic effect. Besides, S. chinensis turns out to have more effects including reproductive regulation and immunomodulatory, antimicrobial, antitussive and antiasthmatic, anti-fatigue, antiarthritic, and bone remodeling effects. Both S. chinensis and S. sphenanthera have inhibitory effects on CYP3A and P-gp, which can mediate metabolism or efflux of substrates, and therefore interact with many drugs. CONCLUSIONS: S. chinensis and S. sphenanthera have great similarities. Dibenzocyclooctadiene lignans are regarded to contribute to most of the bioactivities. Schisandrin A-C, schisandrol A-B, and schisantherin A, existing in both S. chinensis and S. sphenanthera but differing in the amount, are the main active components, which may contribute to the similarities and differences. Study corresponding to the traditional use is needed to reveal the deep connotation of the use of S. chinensis and S. sphenanthera as traditional Chinese medicine. In addition, a joint study of S. chinensis and S. sphenanthera can better show the difference between them, which can provide a reference for clinical application. It is worth mentioning that the inhibition of S. chinensis and S. sphenanthera on CYP3A and P-gp may lead to undesirable drug-drug interactions.

Supplemental Dietary Selenohomolanthionine Improve Antioxidant Activity and Immune Function in Weaned Beagle Puppies.

The purpose of this study was to investigate the effects of dietary Selenohomolanthionine (SeHLan) on antioxidant status and immune response in canine parvovirus (CPV) vaccinated puppies. In this study, 30 weaned puppies were randomly divided into six groups: control group (-Se/-Vacc), immunization group (-Se/+Vacc), supplementation of sodium selenite group (SS/+Vacc, 0.35 mg/kg DM), low-dose SeHLan group (SeHLan-L/+Vacc, 0.35 mg/kg DM), mid-dose SeHLan group (SeHLan-M/+Vacc, 1.0 mg/kg DM), and high-dose SeHLan group (SeHLan-H/+Vacc, 2.0 mg/kg DM). The puppies were fed for 42 days and vaccinated with Vanguard Plus 5 on day 0 and day 21. Blood samples were collected on 7, 14, 21, 28, 35, 42 days post-immunization (PI) for determination of antioxidant indicators, lymphocyte proliferation index, serum cytokine concentration (IL-2, IL-4), canine polymorphonuclear neutrophils (PMN) phagocytic function, and the level of CPV antibody titers. The results showed that SeHLan supplementation raised the serum Se concentration and glutathione peroxidase (GSH-Px) activity in a dose-dependent manner (P < 0.05). It also increased the activity of serum superoxide dismutase (SOD) and decreased serum malondialdehyde (MDA) content, especially in SeHLan-M/+Vacc group (1.0 mg/kg DM) (P < 0.01). SeHLan supplementation significantly increased lymphocyte proliferation, IL-2, and IL-4 levels in canine serum, and enhanced phagocytosis of PMN in vaccinated puppies (P < 0.05). Moreover, SeHLan supplementation shortened the CPV antibody production time and increased the CPV antibody titers (P < 0.05). Of note, the beneficial effects of SeHLan were superior to those of SS. In conclusion, dietary SeHLan supplementation improved antioxidant activity, increased CPV antibody titers, and enhanced immune function in puppies after weaning. An appropriate dosage of SeHLan (1~2 mg/kg DM) may confer nutritional benefits in puppies.

Aucklandiae Radix and Vladimiriae Radix: A systematic review in ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR), as commonly used traditional Chinese herbal medicine, were widely used in the treatment of gastrointestinal diseases. The two herbal medicines were warm, pungent and bitter. They entered the spleen, stomach, large intestine and gallbladder meridians, and had the effect of promoting qi circulation to relieve pain. It is usually used for chest and hypochondrium, abdominal fullness and pain, tenesmus, indigestion, and warming the middle to harmonize the stomach in clinically. AIM OF THIS REVIEW: To provide a reference for the identification of traditional use, the material basis of efficacy and preclinical research between AR and VR, this review systematically summarized the similarities and differences in ethnopharmacology, phytochemistry and modern pharmacology. MATERIALS AND METHODS: The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine, master's thesis, doctoral thesis. RESULTS: In the plateau areas of Sichuan Province, VR used to be regarded as substitute or local habit for AR, which is regularly used for chest, abdominal fullness and pain, diarrhea, and other related diseases. In Chinese Pharmacopoeia (ChP) 2020 edition, 145 prescription preparations with AR were collected, such as Xianglian Wan, Muxiang Shunqi Wan, Liuwei Muxiang San. However, only one prescription preparation (Jiuxiang Zhitong Wan) contained VR. Additionally, 237 and 254 chemical components were separately isolated and identified from AR and VR, 69 kinds of compounds were common among them, and the significant differences were presented in sesquiterpene lactones, monoterpenoids, triterpenoids and phenylpropanoids. Moreover, Costunolide (COS) and Dehydrocostus lactone (DEH), two main research objects of modern pharmacology, showed multiple pharmacological activities. Not only could they inhibit the activity of some cancer cells (such as breast cancer and leukemia cells), but they regulated the levels of various inflammatory factors (including TNF-α, NF-κB, IL-1ß, IL-6) and repressed the growth and reproduction of various microorganisms (like Helicobacter pylori, Staphylococcus aureus). CONCLUSION: COS and DEH as the common active components, provide a certain basis for local medicine about the substitution of VR for AR in Sichuan province of China in the past. In addition, the sesquiterpenoids are the main common compounds in AR and VR by collecting and collating a large number of literature and various data websites. Furthermore, AR and VR have significant differences in ethnopharmacology and phytochemistry, especially in sesquiterpene lactones, monoterpenoids, triterpenoids and phenylpropanoids, and are probably viewed as reference of a separate list of AR and VR in Chinese Pharmacopoeia.

Study of the therapeutic effect of raw and processed Vladimiriae Radix on ulcerative colitis based on intestinal flora, metabolomics and tissue distribution analysis.

BACKGROUND: The intestinal flora imbalance and metabolic disorders are closely related to the pathogenesis of ulcerative colitis (UC). As a commonly used herb for the treatment of gastrointestinal diseases, Vladimiriae Radix (VR) has been used for hundreds of years, and its main active ingredients are costunolide (COS) and dehydrocostus lactone (DEH). Clinical usage habits and previous studies have shown that the processed Vladimiriae Radix (pVR) seems to be more suitable for treating bowel disease than the raw Vladimiriae Radix (rVR), but there is still no relevant comparative study. PURPOSE: To investigate the therapeutic effect of rVR and pVR on UC by analyzing the intestinal flora, metabolomics and tissue distribution. METHODS: UC rat models were established to investigate the anti-inflammatory activities of rVR and pVR by enzyme-linked immunosorbent assay (ELISA), and to study their regulation of intestinal flora and metabolism by 16s rRNA gene analysis and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Moreover, the distribution of COS and DEH in UC mouse tissues were also observed by High Performance Liquid Chromatography Mass Spectrometry (HPLC-MS). RESULTS: rVR and pVR reduced tissue damage and the levels of TNF-α, IL-6, IL-1ß, IL-10, TGF-ß and MPO, especially pVR. 16s rRNA gene analysis showed that rVR superior in ameliorating species evenness and restoring the abundance of Lachnospiraceae and Ruminococcaceae, while pVR is better at increasing the richness and the abundance of Prevotellaceae. Metabolomics analysis suggested that rVR regulates the ß-alanine, pantothenic acid and coenzyme A biosynthesis, but pVR regulates more abundant metabolic pathways. The tissue distribution data indicated the accumulation of COS and DEH in the gastrointestinal tract. CONCLUSION: rVR and pVR had obvious therapeutic effect on UC. The potential mechanisms might be regulating abnormal metabolism, affecting the diversity and structure of intestinal flora, and accumulation of COS and DEH in colon.

Electroacupuncture Stimulation Regulates Adipose Lipolysis via Catecholamine Signaling Mediated by NLRP3 Suppression in Obese Rats.

Chronic low-grade inflammation of visceral adipose tissue can cause obesity-associated insulin resistance, leading to metabolic syndrome. However, anti-inflammatory drugs and those for obesity management can lead to serious side effects such as abnormal heart rate and blood pressure. Consequently, this study aimed to explore the therapeutic potential of electroacupuncture stimulation (ES) for obesity and associated chronic inflammation. Sprague-Dawley male rats were fed a high-fat diet (HFD) for ten weeks to build an obesity model, and half of the diet-induced obesity (DIO) rats were received ES. The levels of inflammatory factors were detected by ELISA and qPCR analysis. The nerve-associated macrophages were marked with immunofluorescence staining. The molecular mechanism of NLRP3 inflammasome in ES was determined by the NLRP3 inflammasome activation model. Compared to HDF rats, ES showed decreased body weight and chronic inflammatory damage. Specifically, this occurred via a decrease in monoamine oxidase-A (MAOA) expression, which suppressed noradrenaline degradation. MAOA is expressed in nerve-associated macrophages (NAMs), and ES attenuated NAMs by suppressing the NLRP3 inflammasome. The NLRP3 agonist blocked the noradrenaline degradation-reducing effect of ES, and an increase in lipolysis via the inhibition of the NLRP3 inflammasome attenuated NAMs. Thus, our findings suggest that ES induced lipolysis via activation of the NLRP3 inflammasome in nerve-associated macrophages (NAMs), independently of sympathetic nervous system activity.

Analysis of the similarities and differences between Auclandia and Vladimirae rhizomes by chemical profiling and chemometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR), as traditional Chinese medicine, have been included in many editions of Chinese Pharmacopoeia with similar efficacy such as promoting qi and relieving pain, which are used to treat chest, hypochondriac, abdominal fullness and pain, diarrhea and tenesmus. In most conditions, VR is used to be a substitute of AR or a local habit. However, whether VR could substitute for AR to play a same role in the formulation and clinical applications needs further study. AIM OF THE STUDY: In this study, similarities and differences between AR and VR would be assessed, and possible reasons that may influence the efficacy of the AR and VR would be explained from the perspective of chemical composition. MATERIALS AND METHODS: HPLC-PDA was used to obtain the data of 10 batches of AR and VR, and to establish chemical fingerprint and chemometric analysis. UPLC-ESI-Q-TOF-MS was used to identify the structure of chemical compounds which contributed to the differences between AR and VR. RESULTS: The chemical fingerprint analysis results showed that 20 peaks in common for AR and 26 peaks in common for VR both presented a good similarity (>0.9), and 15 peaks in common for AR and VR also showed a good similarity (>0.9). Nevertheless, chemometric showed AR was distinct from VR and three chemical compounds, which leading to their differences, were identified by UPLC-ESI-Q-TOF-MS. The three chemical compounds were 3ß-acetoxy-11ß-guaia-4 (15),10 (14)-diene-12,6α-olide, 10α,14-epoxy-11ß-guaia-4 (15)-ene-12,6α-olide and costunolide, respectively. CONCLUSION: In general, AR and VR were highly similar, but their differences were deserved to be paid attention to. This research could provide reference for quality control and set a foundation for clinical applications of AR and VR.

Quality assessment and differentiation of Aucklandiae Radix and Vladimiriae Radix based on GC-MS fingerprint and chemometrics analysis: basis for clinical application.

Vladimiriae Radix, a geo-authentic medicinal herb found in Sichuan Province in China, is highly similar in chemical composition and pharmacological activity to Aucklandiae Radix. It is often used in local practice and as a substitute for Aucklandiae Radix in the treatment of gastrointestinal tract diseases. However, Vladimiriae Radix is preferred to Aucklandiae Radix in traditional Chinese medicine in Sichuan. In order to compare the difference in quality between the two species and differentiate them according to their chemical profiles, and further to explain the rationality of using Vladimiriae Radix as a substitute and explore the reason for the medication preference in Sichuan, similarity was evaluated using gas chromatography-mass spectrometry (GC-MS) fingerprinting and chemometric analysis. Volatile compounds were identified by comparing mass spectra with spectral data from the National Institute of Standards and Technology library 14.L (NIST 14.L) and the linear retention indices (RI) with those previously reported. The results showed that the similarity between the samples from Aucklandiae Radix (>96%) was greater than that of Vladimiriae Radix (>80%). In addition, 41 and 38 compounds were identified in 10 batches of Vladimiriae Radix and Aucklandiae Radix, respectively, and 21 compounds were common to both species, of which dehydrocostus lactone and aplotaxene were abundant in both. However, γ-patchoulene, longicyclene, ß-gurjunene, humulene1,2-epoxide, and ß-patchoulene were unique to Vladimiriae Radix, while 4-terpineol, α-ionone, trans-α-bergamotene, γ-selinene, and camphene were characteristic compounds of Aucklandiae Radix. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) suggested that the two species were well differentiated with regard to the level of essential oils. Orthogonal partial least squares discriminant analysis (OPLS-DA) further showed that compounds including costol, aplotaxene, caryophyllene, humulene, and ß-eudesmol, together with the characteristic compounds of the two species, could be regarded as potential markers for differentiation, among which ß-eudesmol, which is richer in Vladimiriae Radix, and ß-patchoulene, which is unique to Vladimiriae Radix, have potential therapeutic effects on gastrointestinal diseases. The results obtained in this study distinguished Vladimiriae Radix and Aucklandiae Radix on a chemical level, and the similarity in chemical constituents may provide a basis for the rationality of Vladimiriae Radix as a substitute, while ß-patchoulene and ß-eudesmol existing in Vladimiriae Radix provide a theoretical basis for its preferential use in Sichuan. The analysis method established here has important implications for the quality control and differentiation of Vladimiriae Radix and Aucklandiae Radix, which can also serve as a reference for the identification of similar species. Graphical abstract.