Clinical Effect of Mudan Granule on Peripheral Neuritis Caused by Chronic Renal Insufficiency.

Objective: To investigate the clinical effect of Mudan granule on peripheral neuritis caused by chronic renal insufficiency (CRI). Methods: Sixty patients with peripheral neuritis caused by CRI treated in our hospital were included from February 2018 to April 2021 in this study. The patients were arbitrarily assigned into control group and study group. The former accepted routine treatment, while the latter accepted Mudan granule treatment. The clinical efficacy, traditional Chinese medicine (TCM) clinical symptom score, nerve conduction velocity, hemorheology index, renal function index, and inflammatory factor index were compared. Results: We firstly compared the clinical efficacy: the study group was clinically cured in 22 cases, obviously effective in 5 cases, effective in 3 cases, and ineffective in 1 case, with a total effective rate of 96.67%. The control group was clinically cured in 9 cases, obviously effective in 8 cases, effective in 7 cases, and ineffective in 6 cases, with a total effective rate of 80.00%. The total effective rate of the study group was higher compared to the control group (P < 0.05). Secondly, we compared the TCM clinical symptom scores; before treatment, there exhibited no significant difference (P > 0.05); after treatment, the TCM clinical symptom scores decreased. The clinical symptom score of TCM in the study group was lower compared to the control group (P < 0.05). Compared with the control group, the nerve conduction velocity of left MCV, right MCV, left SCV, and right SCV in the study group were remarkably higher. In terms of the hemorheological indexes, the high-shear whole blood viscosity, low-shear whole blood viscosity, and plasma viscosity in the study group were lower compared with the control group (P < 0.05). Before treatment, there existed no significant difference in renal function indexes, but after treatment, the renal function indexes decreased, and the levels of serum creatinine (SCr), blood urea nitrogen (BUN), and uric acid (UA) in the study group were lower compared to the control group (P < 0.05). Finally, we compared the indexes of inflammatory factors; there existed no significant difference before treatment, but after treatment, the indexes of inflammatory factors decreased in both groups, and the levels of IL-6 and CRP in the study group were lower compared to the control group (P < 0.05). Conclusion: For peripheral neuritis caused by CRI, Mudan granule can remarkably promote the clinical symptoms of TCM and reduce the syndrome score of TCM; moreover, it can remarkably increase the nerve conduction velocity of median nerve and common peroneal nerve and reduce blood viscosity, which is worth popularizing and developing in clinic.

Polyphenols from the flower of Hibiscus syriacus Linn ameliorate neuroinflammation in LPS-treated SH-SY5Y cell.

The flower of Hibiscus syriacus Linn is a well-known traditional Chinese medicine (TCM) and health food in China, which has been used to treat dysentery, vaginal discharge, and hemorrhoids. In this study, five polyphenols (compounds 1-5) and five fatty acids (compounds 6-10) were isolated from the ethanol extract of the flower of H. syriacus. The isolated compounds were characterized by spectroscopic techniques. Polyphenols, an important type of natural product, have variety of biological activities. Here, we employed LPS or H2O2-treated SH-SY5Y cell models to test the neuroprotective effect of compounds 1-10. Results found compounds 1-5 (concentration range was around 20 µM on LPS model, concentration range was around 13 µM on H2O2 model), not compounds 6-10, exhibited neuroprotective effect in LPS or H2O2-treated SH-SY5Y cell. PCR analysis showed that compounds 1-5 can effectively improve the mRNA expression of synapse-related gene and neurotrophic factors (Syp, NGF and BDNF) in LPS-treated SH-SY5Y cell. In addition, compounds 1-5 decreased the levels of ROS and MDA and increased the activities of SOD, GSH-Px and CAT in LPS-treated SH-SY5Y cell. Furthermore, compounds 1-5 inhibited neuroinflammation (TNF-α, IL-1ß and IL-6) in LPS-treated SH-SY5Y cell. In conclusion, the polyphenols in the flower of H. syriacus could be a promising candidate for preventive effect of neuroinflammation.

Geraniol Induces Antinociceptive Effect in Mice Evaluated in Behavioural and Electrophysiological Models.

Geraniol (GER) is a monoterpene alcohol with various biochemical and pharmacological properties present in the essential oil of more than 160 species of herbs (especially the Cymbopogon genus). In this study, we evaluated the antinociceptive activity of GER in behavioural and electrophysiological in vitro experimental models of nociception using male Swiss mice. GER (12.5, 25 or 50 mg/kg i.p. and 50 or 200 mg/kg p.o.) reduced the number of writhes induced by acetic acid. The opioid antagonist naloxone (5 mg/kg s.c.) administered in mice subsequently treated with GER (25 mg/kg i.p.) did not reverse such antinociceptive activity, suggesting a non-opioid pathway for the mechanism of action. GER (12.5, 25 and 50 mg/kg i.p.) reduced paw licking time in the second phase of the formalin test. Also, in the glutamate test, GER when administered 50 mg/kg i.p. reduced paw licking time, probably modulating glutamatergic neurotransmission. GER blocked reversibly components of the compound action potential (CAP) recorded in isolated sciatic nerve in a concentration- and drug exposure time-dependent manner: 1 mM to 120 min. for the first component and 0.6 mM to 90 min. for the second component. The IC50 was calculated for the peak-to-peak amplitude (PPA) at 0.48 ± 0.04 mM. The conduction velocity was also reduced by exposure to GER starting from the concentration of 0.3 mM for both components of the CAP. In conclusion, it is suggested that GER has antinociceptive activity, especially in pain related to inflammation, and in part related to reduced peripheral nerve excitability.

Identification and in vitro Evaluation of Lipids from Sclerotia of Lignosus rhinocerotis for Antioxidant and Anti-neuroinflammatory Activities.

Lignosus rhinocerotis (Cooke) Ryvarden (Tiger milk mushroom) is traditionally used to treat inflammation triggered symptoms and illnesses such as cough, fever and asthma. The present study evaluated the in vitro antioxidant, cytotoxic and anti-neuroinflammatory activities of the extract and fractions of selerotia powder of L. rhinocerotis on brain microglial (BV2) cells. The ethyl acetate fraction had a total phenolic content of 0.30 ± 0.11 mg GAE/g. This fraction had ferric reducing capacity of 61.8 ± 1.8 mg FSE/g, ABTS·+ scavenging activity of 36.8 ± 1.8 mg TE/g and DPPH free radical scavenging activity of 21.8% ± 0.7. At doses ranging from 0.1 µg/mL - 100 µg/mL, the extract and fractions were not cytotoxic to BV2 cells. At 100 µg/mL, the crude hydroethanolic extract and the ethyl acetate fraction elicited the highest nitric oxide reduction activities of 68.7% and 58.2%, respectively. Linoleic and oleic acids were the major lipid constituents in the ethyl acetate fraction based on FID and GC-MS analysis. Linoleic acid reduced nitric oxide production and down regulated the expression of neuroinflammatory iNOS and COX2 genes in BV2 cells.

Astaxanthin offers neuroprotection and reduces neuroinflammation in experimental subarachnoid hemorrhage.

BACKGROUND: Neuroinflammation has been proven to play a crucial role in early brain injury pathogenesis and represents a target for treatment of subarachnoid hemorrhage (SAH). Astaxanthin (ATX), a dietary carotenoid, has been shown to have powerful anti-inflammation property in various models of tissue injury. However, the potential effects of ATX on neuroinflammation in SAH remain uninvestigated. The goal of this study was to investigate the protective effects of ATX on neuroinflammation in a rat prechiasmatic cistern SAH model. METHODS: Rats were randomly distributed into multiple groups undergoing the sham surgery or SAH procedures, and ATX (25 mg/kg or 75 mg/kg) or equal volume of vehicle was given by oral gavage at 30 min after SAH. All rats were sacrificed at 24 h after SAH. Neurologic scores, brain water content, blood-brain barrier permeability, and neuronal cell death were examined. Brain inflammation was evaluated by means of expression changes in myeloperoxidase, cytokines (interleukin-1ß, tumor necrosis factor-α), adhesion molecules (intercellular adhesion molecule-1), and nuclear factor kappa B DNA-binding activity. RESULTS: Our data indicated that post-SAH treatment with high dose of ATX could significantly downregulate the increased nuclear factor kappa B activity and the expression of inflammatory cytokines and intercellular adhesion molecule-1 in both messenger RNA transcription and protein synthesis. Moreover, these beneficial effects lead to the amelioration of the secondary brain injury cascades including cerebral edema, blood-brain barrier disruption, neurological dysfunction, and neuronal degeneration. CONCLUSIONS: These results indicate that ATX treatment is neuroprotective against SAH, possibly through suppression of cerebral inflammation.

[Enhanced effect of guizhi plus Gegen Decoction on learning and memory disorder in LPS induced neuroinflammatory mice].

OBJECTIVE: To explore the potential effect of Guizhi plus Gegen Decoction (GGD) in improving learning and memory of lipopolysaccharides (LPS) induced neuroinflammatory mice and its possible mechanisms. METHODS: Totally 63 male ICR mice were randomly divided into 5 groups, i.e., the normal control (n = 13), the model group (n = 13), the low dose GGD group (n = 10), the high dose GGD group (n = 14), and the positive control group (n = 13). Mice were intraperitoneally injected with LPS (0.33 mg/kg) to induce Alzheimer's disease (AD) model. Mice in the high and the low dose GGD groups were administered with 12 g/kg or 6 g/kg by gastrogavage for 4 successive weeks. Mice in the control group were intraperitoneally injected with minocycline (50 mg/kg) for 3 days. By the end of treatment LPS were injected 4 h before behavior test each day, and then behavior test was conducted in mice of each group. Effect of GGD on learning and memory of AD mice was observed by using open field test, novel object recognition task, and Morris water maze. RESULTS: Open field test showed there was no statistical difference in the movement time and the movement distance among all groups (P > 0.05), suggesting that LPS and GGD had no effect on locomotor activities of mice. In novel object recognition test, AD mice spent significantly shorter time to explore novel object after they were induced by LPS (P < 0.05), while for AD mice in the low and high dose GGD groups, their capacities for exploration and memory were significantly improved (P < 0. 05, P < 0.01). Results of Morris water maze showed that AD mice exhibited increased escape latency (P < 0.05) and spent much less time in swimming across the original platform (both P < 0.05). However, AD mice in the low and high dose GGD groups had obvious shortened latency and increased time percentage for swimming (P < 0.05, P < 0.01). CONCLUSION: GGD possessed certain improvement in learning and memory disorder of LPS induced AD mice.

Furanodien-6-one from Commiphora erythraea inhibits the NF-κB signalling and attenuates LPS-induced neuroinflammation.

We investigated the in vitro anti-inflammatory activity of 1(10),4-furanodien-6-one, one the most active compounds of the hexane extract of Commiphora erythraea (Ehrenb.) Engl., by exposing microglial BV-2 cells to lipopolysaccharide. We showed that furanodien-6-one pre-treatment restored cell viability and ROS to control levels while halving NO generation. Production of pro-inflammatory IL-6, IL-23, IL-17, TGF-ß, and INF-γ, significantly induced by LPS, was also markedly reduced by furanodien-6-one treatment. We further showed that furanodien-6-one protects primary neuronal cultures against the inflammatory/toxic insults of LPS-treated BV-2 conditioned media, indicating that furanodien-6-one exerts anti-inflammatory/cytoprotective effects in neuronal cells. We then investigated whether furanodien-6-one exerts anti-inflammatory properties in an in vivo model of microglial activation. In adult mice ip-injected with LPS we found that furanodien-6-one had strong cerebral anti-inflammatory properties by inhibiting liver and brain TNFα as well as IL-1ß expression. Results were not unexpected since FTIR-metabolomic analyses showed that furanodien-6-one-treated mice had a reduced dissimilarity to control animals and that the response to LPS treatment was markedly modified by furanodien-6-one. In conclusion our data provide strong evidence of the anti-inflammatory properties of furanodien-6-one that could be exploited to counteract degenerative pathologies based on neuroinflammation.

Anti-inflammatory and analgesic effects of yaotuitong capsules in experimental rats with chemically induced radicular neuritis.

OBJECTIVE: The aims of this study were to determine the anti-inflammatory and analgesic effects of Yaotuitong (translation: low back and leg pain) capsules, a Chinese herbal preparation, and the histological changes it induces in experimental rats with chemically induced radicular neuritis. METHODS: Wistar rats were randomly divided into normal, model, Western medicine, and traditional Chinese medicine groups (n=24 per group). We surgically duplicated a chemical radicular neuritis model to simulate lumbar intervertebral disc protrusion. Granuloma formation was measured on postoperative days (PODs) 3, 7, 14, and 21. Prostaglandin E2 and 5-hydroxytryptamine (inflammation mediators) levels in the surrounding tissue and the histology of the nerve root were determined on PODs 7 and 14. RESULTS: Yaotuitong capsules significantly reduced prostaglandin E2 (P<0.01) and 5-hydroxytryptamine (P<0.01) levels in tissue surrounding the nerve root. It also inhibited granuloma formation (P<0.05). CONCLUSION: Yaotuitong capsules have anti-inflammatory and analgesic effects that can alleviate the discomfort of lumbar intervertebral disc protrusion.

[Botulinum toxin and painful peripheral neuropathies: what should be expected?]. / Toxine botulique et douleur des neuropathies périphériques : que peut-on en attendre ?

Botulinum toxin type A (BTX-A) is a potent neurotoxin that blocks acetylcholine release from presynaptic nerve terminals by cleaving the SNARE complex. BTX-A has been reported to have analgesic effects independent of its action on muscle tone. The most robust results have been observed in patients with neuropathic pain. Neuropathic pain due to peripheral lesions has been the most widely studied. BTX-A has shown its efficacy on pain and allodynia in various animal models of inflammatory neuropathic pain. The only randomized, double-blind, placebo-controlled trial in patients with focal painful neuropathies due to nerve trauma or postherpetic neuralgia demonstrated significant effects on average pain intensity from 2 weeks after the injections to 14 weeks. Most patients reported pain during the injections, but there were no further local or systemic side effects. The efficacy of BTX-A in painful peripheral neuropathies has been more recently studied. Results were positive in the only study in an animal model of peripheral neuropathy. One study in patients with diabetic painful peripheral neuropathy demonstrated a significant decrease in Visual Analog Scale. In conclusion, one session of multiple intradermal injection of BTX-A produces long-lasting analgesic effects in patients with focal painful neuropathies and diabetic neuropathic pain, and is particularly well tolerated. The findings are consistent with a reduction of peripheral sensitisation, the place of a possible central effect remaining to define. Further studies are needed to assess some important issues, i.e. BTX-A efficacy in patients with small fiber neuropathies and the relevance of early and repeated injections. Future studies could also provide valuable insights into pathophysiology of neuropathic pain.

The emerging role of docosahexaenoic acid in neuroinflammation.

Epidemiological studies have linked fish consumption to lower rates of neurological diseases. Fish contains high levels of omega-3 polyunsaturated fatty acids (n-3 PUFA), and several lines of evidence suggest that the n-3 PUFA docosahexaenoic acid (DHA; 22:6n-3) acts in the brain via anti-apoptotic and neurotrophic pathways. In addition, DHA may act through anti-neuroinflammatory pathways, as DHA possesses anti-inflammatory properties in the periphery. Evidence from animal models has indicated that DHA and its derivatives (resolvin D1 and protectin D1) attenuate colitis, peritonitis and ischemic stroke. n-3 PUFA deprivation in rats decreases brain levels of DHA and increases markers of the brain arachidonic acid (20:4n-6) cascade, a proinflammatory pathway. Thus, chronic low intake of n-3 PUFA may predispose the brain to weak anti-inflammatory, as well as strong proinflammatory signals. Neurological disorders, including Alzheimer's disease, Parkinson's disease and major depression, display a neuroinflammatory component. n-3 PUFA supplementation, as well as drugs targeting brain PUFA metabolism, are promising candidates in the prevention and treatment of neurological disorders.

[Drug-induced toxic hepatitis]. / Medikamentös-toxische Hepatitis.

A 55-year-old male patient was hospitalized with severe nausea, vomiting and icterus. Laboratory testing showed hepatocellular damage. After exhaustive testing, the exclusion diagnosis of a toxic hepatitis was reached. There was a strong temporal correlation with the ingestion of Hong Hua 29, a preparation from Traditional Chinese Medicine (TCM). This medication had been started twelve days prior to the first appearance of symptoms. The existing drug regimen included gabapentin (Neurontin), esomeprazole (Nexium) and prednisone (Prednison Streuli) for the therapy of an acute sensory and motor neuropathy of unknown aetiology. After cessation of Hong Hua 29, gabapentin and esomeprazole, transaminase levels started to declined and normalized within three months. According to the Swissmedic criteria of imputability, a causal correlation between the observed symptoms and the administration of Hong Hua 29 is possible.

Brain-derived neurotrophic factor as a drug target for CNS disorders.

Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of trophic factors. BDNF is widely and abundantly expressed in the CNS and is available to some peripheral nervous system neurons that uptake the neurotrophin produced by peripheral tissues. BDNF promotes survival and differentiation of certain neuronal populations during development. In adulthood, BDNF can modulate neuronal synaptic strength and has been implicated in hippocampal mechanisms of learning and memory and spinal mechanisms for pain. Several CNS disorders are associated with a decrease in trophic support. As BDNF and its high affinity receptor are abundant throughout the whole CNS, and BDNF is a potent neuroprotective agent, this trophic factor is a good candidate for therapeutic treatment of some of CNS disorders. This review aims to correlate the features of some CNS disorders (Parkinson's disease, Alzheimer's disease, depression, epilepsy and chronic pain) to changes in BDNF expression in the brain. The cellular and molecular mechanism by which BDNF might be a therapeutic strategy are critically examined.

Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T.

Subunit non-selective N-methyl-D-aspartate (NMDA) receptor antagonists reduce injury-induced pain behavior, but generally produce unacceptable side effects. In this study, we examined the antinociceptive and motor effects of cone snail venom-derived peptides, conantokins G and T (conG and conT), which are selective inhibitors of the NR2B or NR2A and NR2B subtypes of the NMDA receptor, respectively. We tested the effects of conG and conT in models of tissue (formalin test), nerve injury (partial sciatic nerve ligation) and inflammation-induced (intraplantar Complete Freund's Adjuvant; CFA) pain in mice. In the formalin test, intrathecal (i.t.) conG or conT suppressed the ongoing pain behavior (ED(50) and 95% confidence intervals (CI), 11 (7-19) and 19 (11-33), respectively) at doses that were 17-27 times lower than those required to impair motor function (accelerating rotarod treadmill test: ED(50) and 95% CI, 300 (120-730) and 320 (190-540) pmol, respectively). By comparison, SNX-111, an N-type voltage-sensitive calcium channel antagonist that is also derived from cone snail venom, produced significant motor impairment at a dose (3.0 pmol, i.t.) that was only partially efficacious in the formalin test. Furthermore, conG reversed the allodynia produced by nerve injury, with greater potency on thermal (ED50 and 95% CI, 24 (10-55) pmol) than on mechanical allodynia (59 (33-105) pmol). Finally, a single dose of conG (100 pmol, i.t.) also reduced CFA-evoked thermal and mechanical allodynia. Taken together, these results demonstrate that conantokins exhibit potent antinociceptive effects in several models of injury-induced pain. The study supports the notion that drugs directed against subtypes of the NMDA receptor, by virtue of their reduced side-effect profile, hold promise as novel therapeutic agents for the control of pain.

[Moot questions and rarely employed means of treatment for severe forms of diphtheria in adults]. / O nekotorykh diskussionnykh voprosakh i redko primeniaemykh metodakh lecheniia tiazheloi formi difterii i ee oslozhnenii u vzroslykh.

The authors of the article consider the issue of employment of some treatment options for the grave forms of diphtheria and complications thereof in adult subjects to be a matter of debate and they report their experience gained with the use of rarely employed but efficient means of remediation. In diphtherial myocarditis concurrent with acute renal failure with a critical uncorrectable decline in myocardial contractility in spite of a progressive necrosis of the renal parenchyma due to an inadequate perfusion and toxic nephrosis an adrenomimetic drug (depamine) is to be prescribed. A ban on administration of glycosides is not to be regarded as a dogma. The question of their prescription needs to be decided on an individual basis with due regard to the duration of the illness, degree of cardiac decompensation, and whether it is conduction/contractility function disorders that prevail. Severe forms of diphtheria, including that complicated by myocarditis, especially concurrent with alcohol intoxication have been shown to be alleviated by intravenous administration of 0.015% sodium hypochlorite solution. In diphtheric polyneuritis it was anticholinesterase agents (neostigmine methylsulfate up to 6 mg daily) in maximum permissible doses that the authors employed in critical cases together with hyperbaric oxygenation and, as a means to improve metabolism,--lecithin and amniocen, a biological stimulant from human placenta.

A phase I/II trial of nimodipine for HIV-related neurologic complications.

BACKGROUND: Few effective treatments are available for AIDS dementia complex (ADC) and HIV-associated neuropathy. However, recent in vitro studies indicate that nimodipine, a voltage-dependent calcium channel antagonist, can prevent HIV-related neuronal injury and may provide a novel form of treatment for these disorders. METHODS: To determine the safety and possible efficacy of this agent, 41 patients with mild to severe ADC, including 19 patients with neuropathy, were entered into the AIDS Clinical Trial Group multicenter, phase-I and phase-II study. Nimodipine at 60 mg p.o., five times daily; 30 mg p.o., three times daily; or placebo was administered for 16 weeks as adjuvant treatment to antiretroviral therapy. RESULTS: Neuropsychological performance at baseline, measured by the composite neuropsychological Z score (NPZ-8), correlated significantly with the ADC stage and with CSF levels of neopterin, a marker of immune activation. No significant differences in toxicity were observed among the three arms. Intent-to-treat analysis showed no significant change in the NPZ-8, although improvement was suggested in the high-dose arm. In addition, a trend toward stabilization in peripheral neuropathy was observed in both nimodipine arms compared with placebo. CONCLUSIONS: Nimodipine and other similar nonantiretroviral agents may provide a safe and promising avenue of treatment for neurologic disorders associated with HIV infection. The results of this study indicate that further clinical trials are warranted.

[Lyme disease with the triad of neurologic manifestations].

A 40-year-old man developed progressive neurologic manifestations following a tick bite with subsequent localized erythema migrans. These manifestations included bilateral sensory radiculoneuritis (T7-12), rectovesical dysfunction, paraparesis, right facial palsy and nuchal rigidity. Both serum and cerebrospinal fluid titers of IgG antibody against Borrelia burgdorferi were 1:8,192 using indirect immunofluorescence assay. No IgM antibody was detected. With high-dose intravenous penicillin and corticosteroid treatment the neurologic symptoms and signs gradually subsided, with a corresponding decrease in the IgG antibody titers. Among the cases of Lyme disease reported so far in Japan, the present case seems to be typical and serious in terms of the severity of nervous system involvement and the intensity of the antibody response.

Efficacy of BW759 (9-[[2-hydroxy-1(hydroxymethyl)ethoxy]methyl]guanine) against herpes simplex virus type 1 keratitis in rabbits.

A promising new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy] methyl]-guanine (BW759), which is structurally similar to acyclovir, was tested against acute herpetic keratitis in the rabbit ocular model. Topical 1-0.1% BW759 given 3-5x per day gave beneficial results in that corneal epithelial involvement, conjunctivitis, iritis, and corneal clouding were reduced even when chemotherapy was initiated at 3 days postinoculation. Under the same conditions, topical BW759 therapy gave slightly better results than acyclovir, and both were better than idoxuridine therapy. Mortality rate and colonization of the trigeminal ganglia by HSV-1 were unaffected by BW759 therapy. Duration of virus, shed into the tear film was reduced by BW759.