Revealing the clinical effect and biological mechanism of acupuncture in COPD: A review.

BACKGROUND: To provide new ideas for the clinical and mechanism research of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD), this study systematically reviews clinical research and the progress of basic research of acupuncture in the treatment of COPD. METHODS: PubMed and Web of Science databases were searched using acupuncture and COPD as keywords in the last 10 years, and the included literature was determined according to exclusion criteria. FINDINGS: Acupuncture can relieve clinical symptoms, improve exercise tolerance, anxiety, and nutritional status, as well as hemorheological changes (blood viscosity), reduce the inflammatory response, and reduce the duration and frequency of COPD in patients with COPD. Mechanistically, acupuncture inhibits M1 macrophage activity, reduces neutrophil infiltration, reduces inflammatory factor production in alveolar type II epithelial cells, inhibits mucus hypersecretion of airway epithelial cells, inhibits the development of chronic inflammation in COPD, and slows tissue structure destruction. Acupuncture may control pulmonary COPD inflammation through the vagal-cholinergic anti-inflammatory, vagal-adrenomedullary-dopamine, vagal-dual-sensory nerve fiber-pulmonary, and CNS-hypothalamus-orexin pathways. Furthermore, acupuncture can increase endogenous cortisol levels by inhibiting the HPA axis, thus improving airway antioxidant capacity and reducing airway inflammation in COPD. In conclusion, the inhibition of the chronic inflammatory response is the key mechanism of acupuncture treatment for COPD.

Revealing the biological mechanism of acupuncture in alleviating excessive inflammatory responses and organ damage in sepsis: a systematic review.

Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even endanger life. Acupuncture is widely accepted and applied in the treatment of sepsis, and breakthroughs have been made regarding its mechanism of action in recent years. In this review, we systematically discuss the current clinical applications of acupuncture in the treatment of sepsis and focus on the mechanisms of acupuncture in animal models of systemic inflammation. In clinical research, acupuncture can not only effectively inhibit excessive inflammatory reactions but also improve the immunosuppressive state of patients with sepsis, thus maintaining immune homeostasis. Mechanistically, a change in the acupoint microenvironment is the initial response link for acupuncture to take effect, whereas PROKR2 neurons, high-threshold thin nerve fibres, cannabinoid CB2 receptor (CB2R) activation, and Ca2+ influx are the key material bases. The cholinergic anti-inflammatory pathway of the vagus nervous system, the adrenal dopamine anti-inflammatory pathway, and the sympathetic nervous system are key to the transmission of acupuncture information and the inhibition of systemic inflammation. In MODS, acupuncture protects against septic organ damage by inhibiting excessive inflammatory reactions, resisting oxidative stress, protecting mitochondrial function, and reducing apoptosis and tissue or organ damage.

The mechanistic basis for the effects of electroacupuncture on neuropathic pain within the central nervous system.

Nociceptive signaling responses to painful stimuli are transmitted to the central nervous system (CNS) from the afferent nerves of the periphery through a series of neurotransmitters and associated signaling mechanisms. Electroacupuncture (EA) is a pain management strategy that is widely used, with clinical evidence suggesting that a frequency of 2-10 Hz is better able to suppress neuropathic pain in comparison to higher frequencies such as 100 Hz. While EA is widely recognized as a viable approach to alleviating neuralgia, the mechanistic basis underlying such analgesic activity remains poorly understood. The present review offers an overview of current research pertaining to the mechanisms whereby EA can alleviate neuropathic pain in the CNS, with a particular focus on the serotonin/norepinephrine, endogenous opioid, endogenous cannabinoid, amino acid neurotransmitter, and purinergic pathways. Moreover, the corresponding neurotransmitters, neuromodulatory compounds, neuropeptides, and associated receptors that shape these responses are discussed. Together, this review seeks to provide a robust foundation for further studies of the EA-mediated alleviation of neuropathic pain.

Preparation, Synergism, and Biocompatibility of in situ Liquid Crystals Loaded with Sinomenine and 5-Fluorouracil for Treatment of Liver Cancer.

PURPOSE: Transarterial chemoembolization is the preferred treatment for patients with middle and advanced-stage hepatocellular carcinoma (HCC); however, most hepatic artery embolization agents have various disadvantages. The purpose of this study was to evaluate phytantriol-based liquid crystal injections for potential use in treatment of HCC. METHODS: Using sinomenine (SN) and 5-fluorouracil (5-FU) as model drugs, three precursor in situ liquid crystal injections based on phytantriol (P1, P2, and P3) were prepared, and their in vitro biocompatibility, anticancer activity, and drug release investigated, to evaluate their feasibility for use in treatment of HCC. The properties of the precursor injections and subsequent cubic liquid crystal gels were observed by visual and polarizing microscopy, in an in vitro gelation experiment. Biocompatibility was evaluated by in vitro hemolysis, histocompatibility, and cytotoxicity assays. RESULTS: Precursor injections were colorless liquids that formed transparent cubic liquid crystal gels on addition of excess water. The three precursor injections all caused slight hemolysis, without agglutination, and were mildly cytotoxic. Histocompatibility experiments showed that P1 had good histocompatibility, while P2 and P3 resulted in strong inflammatory responses, which subsequently resolved spontaneously. In vitro anti-cancer testing showed that SN and 5-FU inhibited HepG2 cells in a time- and concentration-dependent manner and had synergistic effects. Further, in vitro release assays indicated that all three preparations had sustained release effects, with cumulative release of >80% within 48 h. CONCLUSION: These results indicate that SN and 5-FU have synergistic inhibitory effects on HepG2 cells, which has not previously been reported. Moreover, we describe a biocompatible precursor injection, useful as a drug carrier for the treatment of liver cancer, which can achieve targeting, sustained release, synergistic chemotherapy, and embolization. These data indicate that precursor injections containing SN and 5-FU have great potential for use in therapy for liver cancer.

Conbercept and Ranibizumab Pretreatments in Vitrectomy with Silicone Oil Infusion for Severe Diabetic Retinopathy.

PURPOSE: We compared the efficacies of intravitreal ranibizumab (IVR) and intravitreal conbercept (IVC) as the adjuvant pretreatments for vitrectomy with silicone oil infusion for tractional retinal detachment (TRD) secondary to proliferative diabetic retinopathy. METHODS: This retrospective study comprised 74 patients (79 eyes) who underwent vitrectomy with silicone oil tamponade for diabetic TRD. They received IVC (37 eyes) or IVR (42 eyes) at standard doses 3-5 days preoperatively and were followed up for ∼6 months. Anatomic success rate, intra- and postoperative complications, and visual outcomes were compared between both groups. RESULTS: Initial (IVC vs. IVR: 97% vs. 98%) and final anatomic success rates (100% in each group) and mean visual acuity changes were not significantly different (P = 0.46). Intraoperative complications [iatrogenic retinal breaks (P = 0.58) and intraoperative bleeding (P = 0.66)], postoperative complications [fibrin formation (P = 0.51), postoperative preretinal bleeding (P = 0.88), progressing or persistent neovascular glaucoma (P = 0.63), progressive fibrovascular proliferation (P = 0.93), and recurrent retinal detachment (P = 0.93)], and surgical variables [surgical time (P = 0.53)] were similar between both groups. CONCLUSIONS: Conbercept and ranibizumab are equally effective surgical adjuvants for vitrectomy with silicone oil infusion in patients with diabetic TRD.

[Rheological properties of sinomenine in situ liquid crystal as liquid embolic agent].

Three different kinds of sinomenine in situ liquid crystal were prepared for different prescriptions, to investigate the rheological properties before and after in situ treatment and evaluate its feasibility for embolization. Rheological experiments were carried out with cone plate fixtures. Both the steady-state rheological and non-steady-state rheological properties of in-situ gels and the swelling gels were studied and compared. Steady-state rheological study results showed that all the three liquid embolic agents were non-newtonian fluid before and after in situ treatment, which would become less ropy when they were pressed with shear stress; their viscosities differed by 2-5 orders of magnitude. It had a yield value of about 10 Pa before in situ treatment and about 4 500 Pa after in situ treatment. All the six systems had thixotropy while their dynamic viscosities were not influenced by the shear rate, all less than 0.3 Pa·s before in situ treatment more than 1 Pa·s after in situ treatment, differing by an order of magnitude. The results of temperature sweeping showed a slight decrease with a steady rate in viscosity within the range of 10-50 °C, differing by 3-4 orders of magnitude. The results of unsteady rheology showed that there was no obvious linear viscoelastic region in the three kinds of agents, indicating the properties of liquid. After in situ treatment, their linear viscoelastic range γ<1% (No.3 was 5%), and their elastic modulus G' was larger than the viscous modulus G", indicating the properties of solid. Frequency scanning results showed that for the systems at low frequencies, G">G', system viscosity in a dominant position; while at high frequencies, G'>G", system elasticity in a dominant position. The results of compound viscosity test also proved that the liquid embolic agent in situ can form a cubic liquid crystal (the structure of No. 3 was destroyed after in situ treatment). The DHR-2 rheometer was used to investigate the rheological properties of in situ gels with three different prescriptions. The method is simple and the result is reliable, which can provide more theoretical reference for the in vitro evaluation and practical application of the product.

Mechanism-based inactivation of cytochrome P450 2B6 by isopsoralen.

1. Isopsoralen (IPRN) is a major component in many traditional medicinal herbs widely used in Asian countries. The objective of the present study was to investigate the inhibitory effect of IPRN on cytochrome P450 2B6 (CYP2B6) and the mechanism involved in the enzyme inactivation. 2. Pre-incubation of CYP2B6 with IPRN resulted in a time- and concentration-dependent enzyme activity loss. The values of K(I) and k(inact) were found to be 7.89 µM and 0.067 min(-1), respectively. Ticlopidine exhibited protective effect on the IPRN-induced enzyme inactivation. The estimated partition ratio of the inactivation was 122. The GSH trapping experiments indicate that an epoxide and/or γ-ketoenal intermediate were/was generated in IPRN-fortified microsomal incubations. The synthetic work verified the formation of the reactive intermediate(s). Additionally, CYPs2E1, 2C19, 2B6 and 1A2 were found to be the major enzymes participating in the bioactivation of IPRN. 3. IPRN was characterized as a mechanism-based inactivator of CYP2B6. An IPRN-derived furanoepoxide and/or γ-ketoenal intermediate(s) were/was generated and may be responsible for the inactivation of CYP2B6.

Mechanism-based inactivation of cytochrome P450 2B6 by isoimperatorin.

Isoimperatorin (IIMP), a 6,7-furanocoumarin derivative, occurs in many common medicinal herbs. Human exposure to IIMP mainly results from intake of fruits, foods and medicinal herbs. We examined the irreversible inhibitory effect of IIMP on cytochrome P450 2B6. IIMP was found to cause time-dependent inhibition of CYP2B6. In addition, the loss of CYP2B6 activity occurred in a NAPDH- and concentration-dependent manner. About 60% of activity of CYP2B6 was suppressed after its incubation with IIMP at 25 µM for 9 min. Enzyme kinetic studies were performed, kinact for IIMP was found to be 0.071 min(-1), and KI was 17.1 µM, respectively. Glutathione and catalase/superoxide dismutase showed little protective effects on CYP2B6 against the inactivation by IIMP. S-Mephenytoin, a substrate of CYP2B6, mildly prevented the enzyme from the inactivation induced by IIMP. The estimated partition ratio of the inactivation was approximately 211. Additionally, a γ-ketoenal intermediate was identified in microsomal incubations with IIMP. CYPs 2B6, 2D6, and 1A2 were the major enzymes responsible for the metabolic activation of IIMP. In conclusion, IIMP is a mechanism-based inactivator of CYP2B6. The formation of γ-ketoenal intermediate may be responsible for the enzyme inactivation.

Imperatorin is a mechanism-based inactivator of CYP2B6.

Imperatorin (IMP) is the major active ingredient in many common medicinal herbs. We examined the irreversible inhibitory effect of IMP on CYP2B6. IMP produced a time- and concentration-dependent inactivation of CYP2B6. About 70% of activity of CYP2B6 was suppressed after its incubation with 1.5 µM IMP for 9 minutes. KI and kinact were found to be 0.498 µM and 0.079 min(-1), respectively. The loss of CYP2B6 activity required the presence of NADPH. Glutathione and catalase/superoxide dismutase showed little protection against the IMP-induced enzyme inactivation. Ticlopidine, a substrate of CYP2B6, showed protection of the enzyme against the inactivation induced by IMP. The estimated partition ratio of the inactivation was approximately 4. Additionally, a γ-ketoenal intermediate was identified in microsomal incubations with IMP. CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 were found to be involved in bioactivation of IMP. In conclusion, IMP is a mechanism-based inactivator of CYP2B6. The formation of γ-ketoenal intermediate may account for the enzyme inactivation.