Integrated therapeutic plasma exchange and traditional Chinese medicine treatment in a patient with severe COVID-19: A case report.

This report presents the case of a 59-year-old man with severe COVID-19 that gradually progressed to cytokine release syndrome and then acute respiratory distress syndrome; he was successfully treated via integration of therapeutic plasma exchange and traditional Chinese medicine. The patient initially presented with a sore throat, severe muscle aches, productive cough and fever. On the worsening of symptoms, remdesivir was administered. However, as the symptoms continued to worsen and a cytokine release syndrome was suspected, oxygen was provided through a high-flow nasal cannula (50 L/min) and therapeutic plasma exchange was performed to prevent worsening of the acute respiratory distress syndrome. On the same day, a course of traditional Chinese medicine was introduced in consultation with the infectious house staff. The patient's symptoms gradually improved; the levels of C-reactive protein and D-dimers reduced, and the patient was weaned to a simple oxygen mask and eventually to room air. This is the first reported case of the integration of these treatments. Together, they prevented the patient from requiring intubation, played a role in cytokine management, and also improved the clinical symptoms, including productive purulent sputum, cough, frequent stool passage and intermittent fever, with no adverse effects. As a result, the patient was discharged within two weeks of the integration of these treatments. Therefore, the integration of therapeutic plasma exchange and traditional Chinese medicine is an effective therapy for patients with severe COVID-19.

Early intervention combining Chinese and Western medicine in traumatic brain injury with diffuse axonal injury: A report of three cases.

BACKGROUND: Traumatic brain injury (TBI) is characterized by high prevalence, morbidity, and mortality. Diffuse axonal injury (DAI) is a specific type of TBI leading to prolonged consciousness impairment and disability. There is still no standard treatment for DAI, so we introduced traditional Chinese medicine into the treatment of these patients. CASE SUMMARIES: Three patients had TBI after traffic accidents. Their Glasgow Coma Scale (GCS) scores in the intensive care unit (ICU) were E1VEM2-3, E1VEM2-3, and E1VEM2 respectively. All of them were diagnosed with DAI based on magnetic resonance imaging (MRI). Because of continuing consciousness disturbances, their families agreed to combine traditional Chinese medicine and modern medicine treatments through inpatient consultation in Taoyuan General hospital. Two patients took Buyang Huanwu Decoction, and one Tianma Gouteng Decoction twice a day. All of them received 20 min of acupuncture treatments 5 times per week. Acupuncture points included Baihui (GV20), Sishencong (EX-HN1), Shuigou (GV26), Hegu (LI4), and Taichong (LR3). All of them started Traditional Chinese medicine treatment within 2 weeks after TBI. The GCS of all three patients recovered to E4M5V6. CONCLUSIONS: The early addition of traditional Chinese medicine treatments to Western medical care can improve the prognosis of patients with diffuse axonal injury.

Prescription of Chinese herbal products is associated with a decreased risk of uterine fibroids: A population-based cohort study.

The finding of a decrease in subsequent fibroid-related operation following the use of Chinese herbal products (CHPs) has led to speculation that CHPs might play a role in uterine fibroids prevention.This study provides an overview of uterine fibroids incidence, comparing CHP users with those who do not use CHPs, referred to as non-CHP users. The results can provide information to clinicians for counseling women about the preventive use of CHPs.A total of 52,151 women (20-45 years of age) were recruited from a nationwide 1-million-person representative sample of those covered by National Health Insurance in Taiwan and were followed from 2000 to 2013. Exact matching was performed for comparative analysis. The age-specific hazard ratios (HRs) of uterine fibroids in relation to either CHP or the phytoestrogen use were calculated with multivariate Cox proportional hazard regression.More than 71% of patients had used a CHP at some point previously. The overall incidence density rate of uterine fibroids for non-CHP users was estimated at 27.5 per 1000 patient-years. The corresponding values for CHP and the phytoestrogen users were lower than those of the non-CHP group (CHP group = 15.5; the phytoestrogen group = 12.5 per 1000 patient-years). The covariate adjusted HRs for uterine fibroid were 0.73 (95% confidence interval [CI] 0.63-0.85) and 0.65 (95% CI 0.52-0.82) in women using CHPs and the phytoestrogen, respectively.CHPs seem to contribute to a decreased risk in developing uterine fibroids. Although the mechanism of action of these products is unclear, their use as a preventive agent for uterine fibroids might be taken into consideration.

Common and unique mechanisms of Chinese herbal remedies on ischemic stroke mice revealed by transcriptome analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Four traditional Chinese herbal remedies (CHR) including Buyang Huanwu decoction (BHD), Xuefu Zhuyu decoction (XZD), Tianma Gouteng decoction (TGD) and Shengyu decoction (SYD) are popular used in treating brain-related dysfunction clinically with different syndrome/pattern based on traditional Chinese medicine (TCM) principles, yet their neuroprotective mechanisms are still unclear. MATERIALS AND METHODS: Mice were subjected to an acute ischemic stroke to examine the efficacy and molecular mechanisms of action underlying these CHR. RESULTS: CHR treatment significantly enhanced the survival rate of stroke mice, with BHD being the most effective CHR. All CHR were superior to recombinant tissue-type plasminogen activator (rt-PA) treatment in successfully ameliorating brain function, infarction, and neurological deficits in stroke mice that also paralleled to improvements in blood-brain barrier damage, inflammation, apoptosis, and neurogenesis. Transcriptome analyses reveals that a total of 774 ischemia-induced probe sets were significantly modulated by four CHR, including 52 commonly upregulated genes and 54 commonly downregulated ones. Among them, activation of neurogenesis-associated signaling pathways and down-regulating inflammation and apoptosis pathways are key common mechanisms in ischemic stroke protection by all CHR. Besides, levels of plasma CX3CL1 and S100a9 in patients could be used as biomarkers for therapeutic evaluation before functional recovery could be observed. CONCLUSION: Our results suggest that using CHR, a combinatory cocktail therapy, is a better way than rt-PA for treating cerebral ischemic-associated diseases through modulating a common as well as a specific group of genes/pathways that may partially explain the syndrome differentiation and treatment principle in TCM.

Unique mechanisms of sheng yu decoction ( shèng yù tang) on ischemic stroke mice revealed by an integrated neurofunctional and transcriptome analysis.

Sheng Yu Decoction ( Shèng Yù Tang; SYD) is a popular traditional Chinese medicine (TCM) remedy used in treating cardiovascular and brain-related dysfunction clinically; yet, its neuroprotective mechanisms are still unclear. Here, mice were subjected to an acute ischemic stroke to examine the efficacy and mechanisms of action of SYD by an integrated neurofunctional and transcriptome analysis. More than 80% of the mice died within 2 days after ischemic stroke with vehicle treatment. Treatments with SYD (1.0 g/kg, twice daily, orally or p.o.) and recombinant thrombolytic tissue plasminogen activator (rt-PA; 10 mg/kg, once daily, intravenously or i.v.) both significantly extended the lifespan as compared to that of the vehicle-treated stroke group. SYD successfully restored brain function, ameliorated cerebral infarction and oxidative stress, and significantly improved neurological deficits in mice with stroke. Molecular impact of SYD by a genome-wide transcriptome analysis using brains from stroke mice showed a total of 162 out of 2081 ischemia-induced probe sets were significantly influenced by SYD. Mining the functional modules and genetic networks of these 162 genes revealed a significant upregulation of neuroprotective genes in Wnt receptor signaling pathway (3 genes) and regulation of cell communication (7 genes) and downregulation of destructive genes in response to stress (13 genes) and in the induction of inflammation (5 genes), cytokine production (4 genes), angiogenesis (3 genes), vasculature (6 genes) and blood vessel (5 genes) development, wound healing (7 genes), defense response (7 genes), chemotaxis (4 genes), immune response (7 genes), antigen processing and presenting (3 genes), and leukocyte-mediated cytotoxicity (2 genes) by SYD. Our results suggest that SYD could protect mice against ischemic stroke primarily through significantly downregulating the damaging genes involved in stress, inflammation, angiogenesis, blood vessel formation, immune responses, and wound healing, as well as upregulating the genes mediating neurogenesis and cell communication, which make SYD beneficial for treating ischemic stroke.

Preventive effect of silymarin in cerebral ischemia-reperfusion-induced brain injury in rats possibly through impairing NF-κB and STAT-1 activation.

Silymarin and silibinin are bioactive components isolated from Silybum marianum. They have been reported to exhibit anti-oxidative and anti-inflammatory effects. Many studies revealed that drugs with potent anti-inflammatory potential can protect animals against inflammation-associated neurodegenerative disease, e.g., stroke. In this current work we established an animal model of acute ischemic stroke injury by inducing cerebral ischemic/reperfusion (CI/R) in rats to elucidate whether silymarin or silibinin can protect animals from CI/R injury. Pretreatment with silymarin, but not silibinin, dose-dependently (1-10µg/kg, i.v.) reduced CI/R-induced brain infarction by 16-40% and improved neurological deficits in rats with a stroke. Elevated pathophysiological biomarkers for CI/R-induced brain injury, including lipid peroxidation, protein nitrosylation, and oxidative stress, were all reduced by silymarin. In addition, expression of inflammation-associated proteins (e.g., inducible nitric oxide synthase, cyclooxygenase-2 and myeloperoxidase), and transcriptional factors (e.g., nuclear factor (NF)-kappa B and signal transducer and activator of transcription (STAT)-1), as well as production of proinflammatory cytokine (e.g., interleukin-1ß and tumor necrosis factor-α) was all significantly prevented by silymarin. Furthermore, an in vitro study on microglial BV2 cells showed that silymarin could inhibit nitric oxide and superoxide anion production, possibly by interfering with NF-κB nuclear translocation/activation. Likewise, silymarin pretreatment also inhibited IκB-α degradation and NF-κB nuclear translocation in brain tissues of ischemic rats. Our results reveal that silymarin, but not its active component silibinin, protected rats against CI/R-induced stroke injury by amelioration of the oxidative and nitrosative stresses and inflammation-mediated tissue injury through impeding the activation of proinflammatory transcription factors (e.g., NF-κB and STAT-1) in the upregulation of proinflammatory proteins and cytokines in stroke-damaged sites. In conclusion, silymarin displays beneficial effects of preventing inflammation-related neurodegenerative disease, e.g., stroke, which needs further investigation and clinical evidences.

Anti-inflammatory ergostanes from the basidiomata of Antrodia salmonea.

Three new anti-oxidative ergostanes, methyl antcinate L (1), antcin M (2), and methyl antcinate K (3), together with nine additional known compounds, 3-ketodehydrosulphurenic acid, sulphurenic acid, dehydrosulphurenic acid, 3beta,15alpha-dihydroxylanosta-7,9(11),24-trien-21-oic acid, zhankuic acid A, zhankuic acid B, zhankuic acid C, antcin C, and antcin K were isolated from the basidiomata of Antrodia salmonea, a newly identified species of Antrodia (Polyporaceae) in Taiwan. These three new compounds were identified as methyl 3alpha,7alpha,12alpha-trihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oate (1), 3alpha,12alpha-dihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oic acid (2), and methyl 3alpha,4beta,7beta-trihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oate (3) by spectroscopic analysis. We studied their antioxidative potential on the production of reactive oxygen species and nitric oxide (NO) in neutrophils and microglial cells, respectively. Compounds 1-3 displayed potent antioxidative activity with IC50 values of around 2.0-8.8 microM that was partially due to inhibition (6-67%) of NADPH oxidase activity but not through direct radical-scavenging properties. Compounds 1-3 also inhibited NO production with IC50 values of around 1.7-16.5 microM and were more potent than a non-specific NOS inhibitor. We conclude that these three new compounds 1, 2, and 3 exhibit anti-inflammatory activities in activated inflammatory cells.

Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells.

Evodia rutaecarpa is commonly used as an anti-inflammatory drug in traditional Chinese medicine. We previously identified four bioactive compounds (dehydroevodiamine (I), evodiamine (II), rutaecarpine (III), and synephrine (IV)) from the ethanol extract of E. rutaecarpa, but their effects and mechanism(s) of action remain unclear. To study the anti-inflammatory potential and the possible underlying mechanism(s), their effects on phorbol-12-myristate-13-acetate (PMA)- and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced reactive oxygen species production in neutrophils was studied, as well as lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible NO synthetase (iNOS) expression in microglial cells. The ethanol extract of E. rutaecarpa displayed potent antioxidative effects against both PMA- and fMLP-induced reactive oxygen species production in neutrophils (with IC50 values of around 2.7-3.3 microg/ml). Although less potent than the ethanol extract of E. rutaecarpa, compounds I-IV all concentration-dependently inhibited PMA- and fMLP-induced reactive oxygen species production, with compound IV consistently being the most potent agent among these active components. The antioxidative effects of the ethanol extract of E. rutaecarpa and these compounds were partially due to inhibition (10%-33%) of NADPH oxidase activity, a predominant reactive oxygen species-producing enzyme in neutrophils, and to a minor extent to their direct radical-scavenging properties. The ethanol extract of E. rutaecarpa also inhibited LPS-induced NO production (with an IC50 of around 0.8 microg/ml) and iNOS upregulation in microglial cells that was partially mimicked by compounds I, II, and III, but not compound IV. Our results suggest that the ethanol extract of E. rutaecarpa and its four bioactive components all exhibited anti-inflammatory activities which could be partially explained by their different potentials for inhibiting NADPH oxidase-dependent reactive oxygen species and/or iNOS-dependent NO production in activated inflammatory cells.

Schisandra chinensis protects against adriamycin-induced cardiotoxicity in rats.

BACKGROUND: Adriamycin (ADR) is an effective chemotherapeutic agent against cancers but its clinical use is limited due to its cardiotoxicity. It has been suggested that the pathogenesis involves inhibition of nucleic acid and protein synthesis, free radical formation and lipid peroxidation. Schisandra (SC) has strong antioxidant activity. We investigate the protective effects of SC on adriamycin-induced cardiotoxicity. METHODS: Wistar rats were divided into four groups: CONT (control), ADR, SC and SC + ADR. After treatment, the hearts of the rats were surgically removed and studied for synthesis rates of nucleic acid and protein, myocardial antioxidants and lipid peroxidation. RESULTS: Cardiotoxicity was characterized by ascites, congested liver and depressed cardiac function. Nucleic acid and protein synthesis were inhibited, malondialdehyde (MDA) was increased, while myocardial glutathione peroxidase (GSHPx) activity and superoxide dismutase (SOD) were decreased by ADR. In contrast, administration of SC before and concurrent with ADR significantly reduced mortality and the amount of ascites. Indexes in myocardial GSHPx, macromolecular biosynthesis and SOD activities increased with a concomitant decrease in lipid peroxidation. CONCLUSION: These results suggest that ADR cardiotoxicity is associated with antioxidant deficit and SC treatment changes the antioxidant status of the heart and improves cardiac function.

New lanostanes and naphthoquinones isolated from Antrodia salmonea and their antioxidative burst activity in human leukocytes.

Four new compounds were isolated from the basidiomata of the fungus Antrodia salmonea, a newly identified species of Antrodia (Aphyllophorales) in Taiwan. These new compounds are named as lanosta-8,24-diene-3beta,15alpha,21-triol (1), 24-methylenelanost-8-ene-3beta,15alpha,21-triol (2), 2,3-dimethoxy-5-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]-naphthoquinone (3), and 2,3-dimethoxy-6-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]-naphthoquinone (4), respectively. Their structures were elucidated by spectroscopic methods. An in vitro cellular functional assay was performed to evaluate their anti-oxidative burst activity in human leukocytes. They showed inhibitory effects against phorbol 12-myristate-13-acetate (PMA), a direct protein kinase C activator, induced oxidative burst in neutrophils (PMN) and mononuclear cells (MNC) with 50 % inhibitory concentration (IC(50)) ranging from 3.5 to 25.8 microM. The potency order of these compounds in PMA-activated leukocytes was as 1 > 3 > 4 > 2. They were relatively less effective in formyl-Met-Leu-Phe (fMLP), a G-protein coupled receptor agonist, induced oxidative burst, except for compounds 3 and 4 in fMLP-activated PMN. These results indicated that three (1, 3, and 4) of these four newly identified compounds displayed anti-oxidative effect in human leukocytes with different potency and might confer anti-inflammatory activity to these drugs.

The inhibitory effect of phenylpropanoid glycosides and iridoid glucosides on free radical production and beta2 integrin expression in human leucocytes.

Rapid production of reactive oxygen species (ROS) and upregulation of beta2 integrin by leucocytes are two important inflammatory responses in human leucocytes. To evaluate whether three phenylpropanoid glycosides (acteoside, crenatoside, and rossicaside B) and two iridoid glucosides (boschnaloside and 8-epideoxyloganic acid) identified from two medicinal plants with similar indications (Orobanche caerulescens and Boschniakia rossica) exhibited anti-inflammatory activity, their effects on N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol-12-myristate-13-acetate (PMA)-activated peripheral human neutrophils (PMNs) and mononuclear cells were examined. Pretreatment with 1-50 microM phenylpropanoid glycoside concentration-dependently diminished PMA- and fMLP-induced ROS production with IC50 values of approximately 6.8-23.9 and 3.0-8.8 muM, respectively. Iridoid glucoside was less effective than phenylpropanoid glycoside with an IC50 value of approximately 8.9-28.4 microM in PMA-activated PMNs and 19.1-21.1 microM in fMLP-activated mononuclear cells. Phenylpropanoid glycosides also effectively inhibited NADPH oxidase (NOX) and displayed potent free radical-scavenging activity, but did not interfere with pan-protein kinase C (PKC) activity. Furthermore, all compounds, except rossicaside B, significantly inhibited PMA- and fMLP-induced Mac-1 (a beta2 integrin) upregulation at 50 microM but not that of fMLP-induced intracellular calcium mobilization. These drugs had no significant cytotoxicity as compared with the vehicle control. Our data suggested that inhibition of ROS production, possibly through modulation of NOX activity and/or the radical scavenging effect, and beta2 integrin expression in leucocytes indicated that these compounds had the potential to serve as anti-inflammatory agents during oxidative stress.