Acupuncture for primary insomnia: Effectiveness, safety, mechanisms and recommendations for clinical practice.

Primary insomnia (PI) is an increasing concern in modern society. Cognitive-behavioral therapy for insomnia is the first-line recommendation, yet limited availability and cost impede its widespread use. While hypnotics are frequently used, balancing their benefits against the risk of adverse events poses challenges. This review summarizes the clinical and preclinical evidence of acupuncture as a treatment for PI, discussing its potential mechanisms and role in reliving insomnia. Clinical trials show that acupuncture improves subjective sleep quality, fatigue, cognitive impairments, and emotional symptoms with minimal adverse events. It also positively impacts objective sleep processes, including prolonging total sleep time, improving sleep efficiency, reducing sleep onset latency and wake after sleep onset, and enhancing sleep architecture/structure, including increasing N3% and REM%, and decreasing N1%. However, methodological shortcomings in some trials diminish the overall quality of evidence. Animal studies suggest that acupuncture restores circadian rhythms in sleep-deprived rodents and improves their performance in behavioral tests, possibly mediated by various clinical variables and pathways. These may involve neurotransmitters, brain-derived neurotrophic factors, inflammatory cytokines, the hypothalamic-pituitary-adrenal axis, gut microbiota, and other cellular events. While the existing findings support acupuncture as a promising therapeutic strategy for PI, additional high-quality trials are required to validate its benefits.

Identifying complementary and alternative medicine recommendations for anxiety treatment and care: a systematic review and critical assessment of comprehensive clinical practice guidelines.

Background: Clinical practice guidelines (CPGs) are used to guide decision-making, especially regarding complementary and alternative medicine (CAM) therapies that are unfamiliar to orthodox healthcare providers. This systematic review aimed to critically review and summarise CAM recommendations associated with anxiety management included in the existing CPGs. Methods: Seven databases, websites of six international guidelines developing institutions, and the National Centre for Complementary and Integrative Health website were systematically searched. Their reporting and methodological quality were evaluated using the Reporting Items for practice Guidelines in Healthcare checklist and the Appraisal of Guidelines for Research and Evaluation (2nd version) instrument, respectively. Results: Ten CPGs were included, with reporting rates between 51.4 and 88.6%. Seven of these were of moderate to high methodological quality. Seventeen CAM modalities were implicated, involving phytotherapeutics, mind-body practice, art therapy, and homeopathy. Applied relaxation was included in 70% CPGs, which varied in degree of support for its use in the treatment of generalised anxiety disorder. There were few recommendations for other therapies/products. Light therapy was not recommended for use in generalised anxiety disorder, and St John's wort and mindfulness were not recommended for use in social anxiety disorder in individual guidelines. Recommendations for the applicability of other therapies/products for treating a specific anxiety disorder were commonly graded as "unclear, unambiguous, or uncertain". No CAM recommendations were provided for separation anxiety disorder, specific phobia or selective mutism. Conclusion: Available guidelines are limited in providing logically explained graded CAM recommendations for anxiety treatment and care. A lack of high-quality evidence and multidisciplinary consultation during the guideline development are two major reasons. High quality and reliable clinical evidence and the engagement of a range of interdisciplinary stakeholders are needed for future CPG development and updating. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373694, identifier CRD42022373694.

Managing depression with complementary and alternative medicine therapies: a scientometric analysis and visualization of research activities.

Background: Complementary and Alternative Medicine (CAM) interventions may prove to be an attractive option for the treatment of depression. The aim of this scientometric analysis is to determine the global scientific output of research regarding managing depression with CAM and identify the hotspots and frontiers within this theme. Methods: Publications regarding the utilization of CAM for treating depression were collected from the Web of Science Core Collection from 1993 to 2022, and analyzed and visualized by Bibliometrix R-package, VOSviewer, and CiteSpace. Results: A total of 1,710 publications were acquired. The number of annual publications showed an overall rapid upward trend, with the figure peaking at 179 in 2021. The USA was the leading research center. Totally 2,323 distinct institutions involving 7,638 scholars contributed to the research theme. However, most of the cooperation was limited to within the same country, institution or research team. The Journal of Alternative and Complementary Medicine was the most productive periodical. The CAM therapies of most interest to researchers were acupuncture and body-mind techniques, such as yoga, meditation and mindfulness. Systematic review and meta-analysis are commonly used methods. "Inflammation," "rating scale" and "psychological stress" were identified as the most studied trend topics recently. Conclusion: Managing depression with evidence-based CAM treatment is gaining attention globally. Body-mind techniques and acupuncture are growing research hotspots or emerging trending topics. Future studies are predicted to potentially investigate the possible mechanisms of action underlying CAM treatments in reducing depression in terms of modulation of psychological stress and inflammation levels. Cross-countries/institutes/team research collaborations should be encouraged and further enhanced.

Identifying complementary and alternative medicine recommendations for insomnia treatment and care: a systematic review and critical assessment of comprehensive clinical practice guidelines.

Background: There is a need for evidence-informed guidance on the use of complementary and alternative medicine (CAM) for insomnia because of its widespread utilization and a lack of guidance on the balance of benefits and harms. This systematic review aimed to identify and summarize the CAM recommendations associated with insomnia treatment and care from existing comprehensive clinical practice guidelines (CPGs). The quality of the eligible guidelines was appraised to assess the credibility of these recommendations. Methods: Formally published CPGs incorporating CAM recommendations for insomnia management were searched for in seven databases from their inception to January 2023. The NCCIH website and six websites of international guideline developing institutions were also retrieved. The methodological and reporting quality of each included guideline was appraised using the AGREE II instrument and RIGHT statement, respectively. Results: Seventeen eligible GCPs were included, and 14 were judged to be of moderate to high methodological and reporting quality. The reporting rate of eligible CPGs ranged from 42.9 to 97.1%. Twenty-two CAM modalities were implicated, involving nutritional or natural products, physical CAM, psychological CAM, homeopathy, aromatherapy, and mindful movements. Recommendations for these modalities were mostly unclear, unambiguous, uncertain, or conflicting. Logically explained graded recommendations supporting the CAM use in the treatment and/or care of insomnia were scarce, with bibliotherapy, Tai Chi, Yoga, and auriculotherapy positively recommended based on little and weak evidence. The only consensus was that four phytotherapeutics including valerian, chamomile, kava, and aromatherapy were not recommended for insomnia management because of risk profile and/or limited benefits. Conclusions: Existing guidelines are generally limited in providing clear, evidence-informed recommendations for the use of CAM therapies for insomnia management due to a lack of high-quality evidence and multidisciplinary consultation in CPG development. More well-designed studies to provide reliable clinical evidence are therefore urgently needed. Allowing the engagement of a range of interdisciplinary stakeholders in future updates of CPGs is also warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369155, identifier: CRD42022369155.

[Toxicity attenuation processing technology and mechanism of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction].

This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.

[Preliminary exploration of detoxification mechanism of processing methods on cardiotoxicity induced by radix Tripterygium wilfordii in mice via Nrf2/HO-1 pathway].

This study aims to investigate the detoxification effects of different processing methods on the cardiotoxicity induced by radix Tripterygium wilfordii, and preliminarily explore the detoxification mechanism via the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1) pathway. The raw and processed products [stir-fried product, product stir-fried with Lysimachiae Herba(JQC), product stir-fried with Phaseoli Radiati Semen(LD), product stir-fried with Paeoniae Radix Alba(BS), product stir-fried with Glycyrrhizae Radix et Rhizoma(GC), and product stir-fried with vinegar(CZ)] of radix T. wilfordii were administrated to mice by gavage at a dose of 2 g·kg~(-1)(based on crude drugs) for 28 days. Twenty-four hours after the last administration, we measured the serum biochemical indexes of mice to evaluate the detoxification effect. Furthermore, we determined the expression of key proteins of Nrf2/HO-1 pathway in mouse heart tissue by Western blot and some oxidation/antioxidation-related indexes by corresponding kits to explore the detoxification mechanism. The administration of the raw product elevated the levels of serum creatine kinase, lactate dehydrogenase, and malondialdehyde, a product of cardiac lipid peroxidation(P<0.01), down-regulated the protein levels of Nrf2 and HO-1(P<0.01), and reduced the levels of total superoxide dismutase, glutathione, glutathione peroxidase, and glutathione S-transferase(P<0.01). However, after the administration of the products stir-fried with JQC, LD, BS, GC, and CZ, the abnormalities of the above indexes induced by the raw product were recovered(P<0.05 or P<0.01). In particular, the product stir-fried with JQC showed the best performance. Taken all together, the cardiotoxicity induced by radix T. wilfordii could be attenuated by stir-frying with JQC, LD, BS, GC, and CZ, and the stir-frying with JQC showed the best detoxification effect. The mechanism might be associated with the cardiac antioxidant defense and oxidative damage mitigation mediated by the up-regulated Nrf2.

Isolation and structural identification of insecticidal compounds from Tripterygium wilfordii.

Five compounds were identified from Tripterygium wilfordii, including two novel compounds and three previously known compounds. Two newly discovered compounds are celangulin CY (1α,2α,3ß,4ß,6ß,8α,13-hepacetoxy-9ß-benzoyloxy-ß-dihydroagarofuran) and celangulin CQ (1α-nicotinoyloxy-2α,3ß,6ß-triacetoxy-9ß-furancarbonyloxy-13-isobutanoyloxy-4ß-hydroxy-ß-dihydroagarofuran). Their structures were determined using nuclear magnetic resonance (NMR), mass spectrometry (MS), and high-pressure liquid chromatography (HPLC). The isolated compounds were tested for insecticidal activity against the third instar larvae of Spodoptera frugiperda. Both celangulin CY and celangulin CQ exhibited significantly higher oral toxicity in the larvae than that exhibited by the three known compounds.

A novel palmitic acid hydroxy stearic acid (5-PAHSA) plays a neuroprotective role by inhibiting phosphorylation of the m-TOR-ULK1 pathway and regulating autophagy.

AIMS: Type 2 diabetes mellitus (T2DM) can lead to brain dysfunction and a series of neurological complications. Previous research demonstrated that a novel palmitic acid (5-PAHSA) exerts effect on glucose tolerance and chronic inflammation. Autophagy was important in diabetic-related neurodegeneration. The aim of the present study was to investigate whether 5-PAHSA has specific therapeutic effects on neurological dysfunction in diabetics, particularly with regard to autophagy. METHODS: 5-PAHSA was successfully synthesized according to a previously described protocol. We then carried out a series of in vitro and in vivo experiments using PC12 cells under diabetic conditions, and DB/DB mice, respectively. PC12 cells were treated with 5-PAHSA for 24 h, while mice were administered with 5-PAHSA for 30 days. At the end of each experiment, we analyzed glucolipid metabolism, autophagy, apoptosis, oxidative stress, cognition, and a range of inflammatory factors. RESULTS: Although there was no significant improvement in glucose metabolism in mice administered with 5-PAHSA, ox-LDL decreased significantly following the administration of 5-PAHSA in serum of DB/DB mice (p < 0.0001). We also found that the phosphorylation of m-TOR and ULK-1 was suppressed in both PC12 cells and DB/DB mice following the administration of 5-PAHSA (p < 0.05 and p < 0.01), although increased levels of autophagy were only observed in vitro (p < 0.05). Following the administration of 5-PAHSA, the concentration of ROS decreased in PC12 cells and the levels of CRP increased in high-dose group of 5-PAHSA (p < 0.01). There were no significant changes in terms of apoptosis, other inflammatory factors, or cognition in DB/DB mice following the administration of 5-PAHSA. CONCLUSION: We found that 5-PAHSA can enhance autophagy in PC12 cells under diabetic conditions. Our data demonstrated that 5-PAHSA inhibits phosphorylation of the m-TOR-ULK1 pathway and suppressed oxidative stress in PC12 cells, and exerted influence on lipid metabolism in DB/DB mice.

9-PAHSA promotes browning of white fat via activating G-protein-coupled receptor 120 and inhibiting lipopolysaccharide / NF-kappa B pathway.

Browning of white adipose tissue is a novel mechanism to counteract obesity in view of its thermogenic activity. Activation of G-protein-coupled receptor 120 (GPR120) can promote the browning of white fat. 9-PAHSA, an endogenous mammalian lipid, which is acting as the ligand of GPR120 to enhance glucose uptake and exert anti-inflammatory effect. In the study, we would like to investigate the biological effects of 9-PAHSA on adipocyte browning. Here, we show that 9-PAHSA induces browning of 3T3-L1 adipocytes via enhanced expression of brown fat specific genes. 9-PAHSA-induced browning in white adipocytes of WT mice and ob/ob mice was investigated by determining expression levels of brown adipocyte-specific genes/proteins by quantitative real-time polymerase chain reaction analysis, immunoblot analysis and immunochemical staining. The effects of 9-PAHSA on brown fat markers in 3T3-L1 cells were decreased when GPR120 gene was silenced. To investigate the molecular mechanism of 9-PAHSA on adipocyte browning, lipopolysaccharide (LPS)-induced inflammatory model was conducted. 9-PAHSA treatment abolished LPS-induced NF-kappa B (NF-κB) activation and inflammatory cytokine secretion. But these anti-inflammatory effects of 9-PAHSA were attenuated by GPR120 knockdown. Our finding demonstrated that the browning of adipocyte was induced by 9-PAHSA through activating GPR120 and inhibiting the LPS/NF-κB pathway. This promising result will help to reveal the potential pathogenesis of obesity.

Triterpenoids and lignans from the fruit of Schisandra sphenanthera.

Three new (1-3) and seven known (4-10) triterpenoids, together with one new (11) and fifteen known (12-26) dibenzocyclooctadiene lignans, were isolated from the fruit of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by extensive analysis of spectroscopic methods, including HRESIMS, 1D and 2D NMR spectra and CD experiments. All of the isolated triterpenoids (1-10) were evaluated for their in vitro cytotoxicities against HepG2 human hepatocellular carcinoma cell line, and compounds 1, 3-7 and 10 exhibited moderate antiproliferative effects against HepG2 cell line with IC50 ranging from 18.12 to 49.52µM. The lignans (11-26) were tested for their neuroprotective activities against CoCl2, H2O2 and Aß25-35-induced SH-SY5Y cell injuries and showed considerable neuroprotective effects of different degrees. And at the low concentration of 3.2nM, compounds 14, 17-19, 23 in CoCl2-induced, compounds 11, 13-15, 17, 19-20, 22-24 in H2O2-induced, and compounds 12-14, 19, 25-26 in Aß25-35-induced SH-SY5Y cell injury models, showed statistically significant neuroprotective activities compared with the negative control group, respectively.

Phytoestrogen α-zearalanol exerts antiapoptotic effects in differentiated pc12 cells via oestrogen receptor α.

Our previous studies have demonstrated that phytoestrogen α-zearalanol (α-ZAL) possesses potential benefits in alleviating cell apoptotic death just like oestrogen. However, the underlying mechanism is not fully understood. This study was designed to test the hypothesis that the neuroprotective effect of α-ZAL is mediated by oestrogen receptor (ER) as α-ZAL owns the benzene ring structure may interact with ER. The present results showed a significant increase in apoptosis in differentiated PC12 cells after a 24-hr exposure to amyloid ß-peptide fragment 25-35 (Aß25-35 ), accompanied by decreasing of bcl-2 expression and increasing bax expression, whereas a pre-treatment with α-ZAL ameliorated these changes induced by Aß25-35 . In addition, the α-ZAL-mediated cytoprotection was abrogated by ERα antagonist but not by ERß antagonist. In summary, these data suggest that α-ZAL intervenes against Aß-induced apoptosis via intersecting bcl-2-bax apoptotic pathway in an ERα-sensitive manner.

In vitro and in vivo evaluation of pectin-based nanoparticles for hepatocellular carcinoma drug chemotherapy.

The fabrication and evaluation of a natural pectin-based drug delivery system are reported in this study. The drug delivery system displays specific active targeting ability to hepatocellular carcinoma due to the presence of excess galactose residues in the polymer structure as the natural targeting ligands. The system was prepared under very mild conditions in an aqueous medium containing Ca(2+) and CO3(2-) ions, generating uniform pectin-based nanoparticles with an average diameter of 300 nm, and the drug-loading content of anticancer drug 5-fluorouracil (5-FU) is around 24.8%. Cytotoxicity study of the 5-FU-loaded nanoparticles (5-FU-NPs) in HepG2 and A549 cell lines demonstrated their greater potency in killing cancer cells with overexpressed asialoglycoprotein receptor (ASGPR) on the cell surface, compared to that of the free drug. Pharmacokinetics study using Sprague-Dawley (SD) rats further confirmed that the drug-loaded nanoparticles showed a much longer half-life in the circulation fluids than the free drug. Tissue distribution was investigated on Kunming mice, and the results also demonstrated that the 5-FU-NPs has a long circulation effect. Taken together, the pectin-based drug delivery systems exhibit size-induced prolonged circulation as well as ASGP receptor-mediated targeting ability to cancer cell lines; therefore, it is a promising platform for the treatment of hepatocellular carcinoma.