[Superiority of motor imagery acupuncture in improving muscle tension for patients with upper limb hemiplegia of stroke in early stage].

OBJECTIVE: To verify the superiority of motor imagery acupuncture in improving muscle tension for patients with upper limb hemiplegia in early stroke. METHODS: A total of 64 patients of stroke hemiplegia with upper limb flaccid paralysis were randomly divided into an observation group (32 cases, 1 case dropped off ) and a control group (32 cases, 4 cases dropped off ). The observation group was treated with motor imagery acupuncture (both acupuncture and motor imagery therapy at affected upper limb were performed).The control group was treated with acupuncture plus motor imagery therapy at affected lower limb, 2 h later after acupuncture, motor imagery therapy was applied to upper limb. Baihui (GV 20) to Taiyang (EX-HN 5) of healthy side, Fengchi (GB 20) and Jianyu (LI 15), Jianjing (GB 21), Quchi (LI 11), Waiguan (TE 5) on the affected side, ect. were selected in both groups, once a day, 5 times a week for 4 weeks. Before and after treatment, 4, 8 weeks after treatment, the modified Ashworth scale (MAS) grade and Brunnstrom stage were compared in the two groups. RESULTS: Compared before treatment, the muscle tension of shoulder, elbow and wrist each time point after treatment was increased in the two groups (P<0.05). After treatment, the proportion less than grade Ⅱ of elbow MAS grade in the observation group was higher than the control group (P<0.05); 4 and 8 weeks after treatment, the proportion less than grade Ⅱ of shoulder, elbow and wrist MAS grades in the observation group was higher than the control group (P<0.01). The Brunnstrom stage of arm and hand each time point after treatment was higher than the previous time point in the two groups (P<0.05), those in the observation group was higher than the control group (P<0.05). CONCLUSION: Motor imagery acupuncture could promote hemiplegia upper limb muscle tension recovery in patients of stroke hemiplegia with upper limb flaccid paralysis, make the patients gradually shift to the separate fine movement mode, inhibit and relieve the appearance and development of spasm.

Uncovering the active components, prospective targets, and molecular mechanism of Baihe Zhimu decoction for treating depression using network pharmacology-based analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Baihe Zhimu decoction (BZD) is a classical traditional Chinese medicinal herbal formula. It consists of two herbal medicines, Rhizoma Anemarrhenae (Zhimu), the rhizomes of Anemarrhena asphodeloides Bge. (Liliaceae), and Bulbus Lilii (Baihe), the bulbs of Lilium brownii var. Viridulum Baker (Liliaceae). BZD has been widely used in China to treat depression and verified to be effective without evident side effects. AIM OF THE STUDY: The aim of this study was to elucidate the active components, potential targets, and molecular mechanism of Baihe Zhimu decoction for treating depression. MATERIALS AND METHODS: In this research, a chronic unpredictable mild stress (CUMS) mice was first established to evaluate the pharmacological effects of BZD for treating depression. A component database was then constructed for BZD. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS) technique was used to identify the components in BZD and blood-absorbed components. Further screening and validation of protein targets were performed by molecule docking. The component-target binding affinity was validated by surface plasmon resonance analysis (SPR) assay. The related pathways were predicted by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Relative proteins in the predicted pathways were finally assessed by Western blot. RESULTS: The pharmacology evaluation experiment demonstrated that BZD could improve depressive-like behavior, inhibit the hippocampal secretion of pro-inflammatory cytokines and reduce neuronal apoptosis in CUMS mice model. A component database containing 163 components and a target database covering 1286 proteins were constructed. HPLC-QTOF-MS assay identified twenty-six components from BZD and ten components absorbed into rat plasma after an intragastric treatment with BZD. Next, 56 underlying targets were screened out by a virtual high-throughput screening approach. Twenty-seven of them were further screened out and confirmed by molecular docking. Afterward, a component-target network was established, and the component-protein binding affinities were validated by SPR assays. By KEGG pathway enrichment analysis, two signaling pathways PI3K/Akt and MAPK were predicted as the potential signaling cascades. Finally, Western blot showed that BZD dramatically reversed the suppression of PI3K/Akt/GSK-3ß pathway and the activation of MAPK pathway in CUMS mice model. CONCLUSIONS: BZD demonstrated a substantial pharmacological effect on CUMS mice model. Network pharmacology-based analysis predicted that ten blood-absorbed components can act on 27 target proteins. KEGG and Western blotting analysis suggested that BZD could exert antidepressant effects by regulating the PI3K/Akt and MAPK signaling pathways.

Effects of acupuncture treatment on motor function in patients with subacute hemorrhagic stroke: A randomized controlled study.

OBJECTIVE: The aim of this study was to evaluate the additional effects of acupuncture treatment on motor function in patients with subacute hemorrhagic stroke. DESIGN: One hundred and thirty-four patients with subacute hemorrhagic stroke were randomized to receive acupuncture treatment plus conventional treatment (treatment group) or conventional treatment only (control group). Acupuncture treatments were given in 24 sessions over 4 weeks, with 3-month follow-up period. Blinded evaluation was based on Fugl-Meyer Assessment, Barthel Index with an intention-to-treat analysis. For those patients who were able to walk, a three-dimensional gait analysis system was employed to objectively record spatiotemporal and kinematic parameters. RESULTS: Compared with control group, the treatment group showed a significantly greater over-time improvement in total Fugl-Meyer, lower-limb Fugl-Meyer, but not in upper-limb Fugl-Meyer and Barthel Index. The spatiotemporal parameters of velocity, step length, cadence, step width all showed significant difference between the 2 groups. The velocity in treatment group decreased unexpectedly at day 14, then increased sharply and overcame control group at day 28. The treatment group also showed a significantly greater increase in peak circumduction, peak hip hiking, hip range of motion, knee range of motion and a tendency for the ankle range of motion. CONCLUSIONS: Acupuncture may promote the motor function recovery of hemorrhagic stroke patients in subacute phase mainly by enhancing the lower limb ability. It probably diminishes the compensation strategies earlier to correct the abnormal gait pattern. Although this adjustment may result in a compromise in the improvement of gait velocity temporarily, patients would benefit from it in a long run.

Effects of Acupuncture Treatment on Lower Limb Spasticity in Patients Following Hemorrhagic Stroke: A Pilot Study.

BACKGROUND AND PURPOSE: Lower limb spasticity is often a significant problem in stoke rehabilitation. The purpose of this study was to investigate the effects of acupuncture treatment on lower limb spasticity in patients following hemorrhagic stroke. METHODS: Fifty-nine patients following hemorrhagic stroke were randomized to receive acupuncture treatment combined with conventional treatment (treatment group [TG]) or conventional treatment only (control group [CG]). Acupuncture treatments were given in 24 sessions over 4 weeks. Blinded evaluation was based on Modified Ashworth Scale (MAS), short intracortical inhibition (SICI), and Hmax/Mmax ratio as the primary outcomes. In addition, Fugl-Meyer Assessment (FMA), Barthel Index (BI), motor evoked potential (MEP) and surface integrated electromyogram (IEMG) were employed as the secondary outcomes. All the evaluations were performed at 14 and 28 days after the start of the treatment. RESULTS: Compared with the CG, the TG showed a significantly greater over-time decrease in MAS for knee (p = 0.022) and ankle (p = 0.017), SICI (p = 0.000) and Hmax/Mmax ratio (p = 0.000). In all patients of TG, we found a greater improvement in lower-limb FMA and MEP but not in BI. IEMG show that TG obtained a greater reduction in spastic agonist muscles and a greater enhancement in spastic antagonist muscles. A significant correlation between a greater decrease in ankle MAS and a greater increase in SICI for spastic muscles was found (r = 0.390, p = 0.002). CONCLUSIONS: Acupuncture could improve the lower limb spasticity and motor function, thus providing a safe and economical approach for treating stroke patients. The potential mechanism underpinning the greater improvement may be attributed to a reshape of corticospinal plasticity induced by acupuncture.

Anti­angiogenic therapy for normalization of tumor vasculature: A potential effect of Buyang Huanwu decoction on nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential.

The present study aimed to investigate the effect of Buyang Huanwu decoction (BYHWD) on tumor growth, metastasis and angiogenesis in nude mice bearing human hepatocellular carcinoma (HCC) HCCLM3 xenografts. A total of 96 nude mice bearing HCCLM3 xenografts were randomly divided into four groups: BYHWD group (LB), Yi­qi decoction group (LY), Huo­xue decoction group (LH) and model group (LM). Each of these groups was divided into three subgroups (n=8), which were observed on days 21, 25, 38 following treatment, respectively. The tumor weights, volumes and pulmonary metastases were recorded. The expression of CD105 and the microvessel density (MVD) were assessed, and the expression levels of vascular endothelial growth factor (VEGF), hypoxia­inducible factor 1α (HIF­1α), and regulator of G protein signaling 5 (RGS­5) were analyzed using immunohistochemical staining. Compared with the LM group, no significant decrease in tumor weight or volume were observed in the herbal medicine treatment groups, the number of the metastases in the lungs decreased, whereas the expression levels of RGS­5 and HIF­1α decreased in the LB group on day 35. However, the expression levels of VEGF increased in the LB group on days 28 and 35 post­treatment. The results of the present study suggested that BYHWD may inhibit angiogenesis and metastasis by affecting the expression levels of VEGF, RGS­5 and HIF­1α, and suggested that BYHWD may contribute to the tumor microenvironment and vasculature normalization in HCC.

Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer.

Natural products, such as fermented soybeans, have been used to treat various physical conditions, including cancer. MB-6 is a botanical preparation composed of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract. Based on this, we hypothesized that MB-6 would increase the effectiveness of chemotherapy in patients with colon cancer. In a rodent study, MB-6, in combination with leucovorin/5-fluorouracil chemotherapy, increased the survival rate and life span of colon cancer tumor-bearing BALB/c mice as compared with treatment with chemotherapy alone. In a proof-of-concept clinical study, 72 patients with metastatic colorectal cancer were randomized to receive leucovorin, 5-fluorouracil, and oxaliplatin in combination with either MB-6 or placebo for 16 weeks. The primary outcome was the best overall response, and secondary outcomes included progression-free survival, overall survival, and adverse effects. Up to 77 weeks after treatment, there was follow-up with the patients. No significant difference in the best overall response rate and overall survival was observed between the 2 groups. Patients in the MB-6 group had a significantly lower disease progression rate than patients in the placebo group, during the study period (0.0% vs 15.8%, P = .026). The placebo group had a significantly higher incidence of adverse events at least grade 4 compared with the MB-6 group (28.9% vs 2.9%, respectively, P = .004) and a significantly higher occurrence of increased serum creatinine compared with the MB-6 group (29% vs 5.9%, P = .014). MB-6 is a promising botanical supplement that may increase the effectiveness of chemotherapy in patients with metastatic colorectal cancer.

Randomized clinical trial of new intravenous lipid (SMOFlipid 20%) versus medium-chain triglycerides/long-chain triglycerides in adult patients undergoing gastrointestinal surgery.

BACKGROUND: SMOFlipid 20% is intravenous lipid emulsion (ILE) containing long-chain triglycerides (LCT), medium-chain triglycerides (MCT), olive oil, and fish oil as a mixed emulsion containing α-tocopherol. The aim was to assess the efficacy of this new ILE in gastrointestinal surgery compared with MCT/LCT. METHODS: In this prospective study, 40 patients were randomized to SMOFlipid 20% or MCT/LCT (Lipovenoes 20%) group. Clinical and biochemistry data were collected. Inflammatory markers (CRP, IL-6, IL-10, TNF-α, TGF-ß1) and oxidative stress (ROS and superoxide) were measured. RESULTS: Thirty-five patients (17 males and 18 females) with a mean age of 57 years completed the study. The patients' demographic characteristics (age, gender, height, body weight, and BMI) were similar without significant differences between groups. The increment of triglyceride on day 6 from baseline was significantly lower in SMOFlipid group than in Lipovenoes MCT/LCT group. Inflammatory markers, as well as superoxide radical and total oxygen radical were not different between groups. CONCLUSIONS: Despite the comparable effect on inflammatory response, because of its well-balanced fatty acid pattern, relatively low n-6:n-3 ratio, and high vitamin E content, SMOFlipid had a better triglyceride-lowering effect as compared with MCT/LCT in adult patients undergoing gastrointestinal surgery.

Effects of Different Doses of Dexamethasone on Bone Mineral Density and Body Composition in Rats / 天津医药

Objective To investigate the effects of different doses of dexamethasone (Dex) on bone mineral density (BMD) and body composition in Sprague-Dawley (SD) rats. Methods Forty 3-month-old female SD rats were divided into four groups:control group (Cont, saline), low dose Dex group (LDG, 1 mg/kg), medium dose Dex group (MDG, 2.5 mg/kg) and high dose Dex group (HDG, 5 mg/kg). Ten rats for each group. Dex was injected intramuscularly twice a week. The values of BMD and body composition were measured by DEXA densitometer at the beginning and 4-week of treatment. Results The body weights of different doses of Dex intervention groups were decreased after 1 to 4-week intervention compared with those of Cont group (P<0.01). After 4-week intervention, the total BMD, femur BMD, total bone mineral content (BMC), to-tal fat mass, trunk fat mass and leg fat mass were significantly increased in Cont group (P<0.01), while the total lean mass, trunk lean mass were significantly decreased (P<0.01). The total BMC, femur BMD, leg lean mass, leg fat mass were signifi-cantly lower in LDG group and MDG group than those of Cont group (P<0.05). The femur BMD, leg fat mass were signifi-cantly lower in LDG group and MDG group than those of HDG group (P<0.05). Conclusion The doses of 1 mg/kg and 2.5 mg/kg Dex have greater impact on the femur BMD and the leg composition in SD rats than that of Dex (dose of 5 mg/kg ).

Inhibition of Metastatic Potential in Breast Carcinoma In Vivo and In Vitro through Targeting VEGFRs and FGFRs.

Angiogenesis and lymphangiogenesis are considered to play key roles in tumor metastasis. Targeting receptor tyrosine kinases essentially involved in the angiogenesis and lymphangiogenesis would theoretically prevent cancer metastasis. However, the optimal multikinase inhibitor for metastasis suppression has yet to be developed. In this study, we evaluated the effect of NSTPBP 0100194-A (194-A), a multikinase inhibitor of vascular endothelial growth factor receptors (VEGFRs)/fibroblast growth factor receptors (FGFRs), on lymphangiogenesis and angiogenesis in a mammary fat pad xenograft model of the highly invasive breast cancer cell line 4T1-Luc(+). We investigated the biologic effect of 194-A on various invasive breast cancer cell lines as well as endothelial and lymphatic endothelial cells. Intriguingly, we found that 194-A drastically reduced the formation of lung, liver, and lymph node metastasis of 4T1-Luc(+) and decreased primary tumor growth. This was associated with significant reductions in intratumoral lymphatic vessel length (LVL) and microvessel density (MVD). 194-A blocked VEGFRs mediated signaling on both endothelial and lymphatic endothelial cells. Moreover, 194-A significantly inhibited the invasive capacity induced by VEGF-C or FGF-2 in vitro in both 4T1 and MDA-MB231 cells. In conclusion, these experimental results demonstrate that simultaneous inhibition of VEGFRs/FGFRs kinases may be a promising strategy to prevent breast cancer metastasis.

Ethanolic Extract of Agaricus blazei Fermentation Product Inhibits the Growth and Invasion of Human Hepatoma HA22T/VGH and SK-Hep-1 Cells.

Hepatoma is a leading cause of death in the world. SK-Hep-1 and HA22T/VGH cells are poorly differentiated human hepatocellular carcinoma cell lines with invasive and migratory abilities. Agaricus blazei (AB) is a mushroom with many biological effects and active ingredients, and the ethanolic extract of AB fermentation product (AB-pE) was demonstrated to inhibit the growth of hepatoma Hep3B and HepG2 cells in our previous study. In this study, we further investigated the anticancer and anti-invasive abctivities of the AB-pE. Results showed that the AB-pE inhibited the growth of SK-Hep1 and HA22T/VGH cells (with IC50 values of 26.8 and 28.7 µg/mL, respectively) and led cells toward apoptosis after 48 h of treatment. Activation of caspase-3 by AB-pE (12.5~200 µg/mL) in a dose-dependent manner was observed in both cell lines using fluorescence microscopy and flow cytometry. The apoptosis triggered by the AB-pE was regulated by the increased expression of Bax, the activation of caspase-3, caspase-9, and PARP, and the decreased expression of Bcl-2. Additionally, the AB-pE showed the potential ability to inhibit invasion of SK-Hep1 and HA22T/VGH cells according to the results of a Matrigel invasion assay. Our results suggested that the AB-pE may be a further developed for its potential against hepatoma due to its antiproliferative (via apoptosis) and anti-invasive activities in hepatoma cells.

Effect of the ethanol extract of Picrorhiza scrophulariiflora on the progression of chronic kidney disease in a rat remnant kidney model / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of the ethanol extract of Picrorhiza scrophulariiflora (EPS) on renal function and tissue damage in a rat remnant kidney model.</p><p><b>METHODS</b>Rat models of chronic kidney disease induced by 5/6 nephrectomy (5/6 Nx) were randomly assigned into two groups for treatment with a gavage of either EPS or vehicle for 9 weeks. The rats in the control group received only sham operation.</p><p><b>RESULTS</b>Compared with vehicle-treated 5/6 Nx rats, the EPS-treated rats displayed significantly decreased urinary excretion of malondialdehyde, serum levels of AGEs and AOPPs, and increased serum SeGSHPx activities. These changes were associated with attenuated urinary protein excretion, glomerular sclerosis and interstitial fibrosis.</p><p><b>CONCLUSION</b>EPS can obviously improve the renal functions and renal pathologies in rats with chronic kidney disease probably by inhibiting the oxidative stress.</p>

Identification of calreticulin as a prognosis marker and angiogenic regulator in human gastric cancer.

The purpose of this study was to identify genes of interest for a subsequent functional and clinical cohort study using complementary (c)DNA microarrays. cDNA microarray hybridization was performed to identify differentially expressed genes between tumor and nontumor specimens in 30 gastric cancer patients. Subsequent functional studies of the selected gene were carried out, including cell cycle analysis, cell migration analysis, analyses of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF), and oligo-microarray studies using two pairs of stable cell lines of the selected gene. Another independent cohort study of 79 gastric cancer patients was conducted to evaluate the clinical significance of the selected gene in human gastric cancer. Calreticulin (CRT) was selected for further investigation. Two pairs of stable cell lines of CRT overexpression and CRT knockdown were constructed to perform functional studies. CRT enhanced gastric cancer cell proliferation and migration. Overexpressed CRT upregulated the expression and secretion of PlGF and VEGF. CRT had a reciprocal effect on connective tissue growth factor (CTGF) expression. Positive immunohistochemical staining of calreticulin was significantly correlated with high microvessel density (MVD) (p = 0.014), positive serosal invasion (p = 0.013), lymph node metastasis (p = 0.002), perineural invasion (p = 0.008), and poor patient survival (p = 0.0014). Multivariate survival analysis showed that CRT, MVD, and serosal invasion were independent prognosticators. We conclude that CRT overexpression enhances angiogenesis, and facilitates proliferation and migration of gastric cancer cells, which is in line with the association of CRT with MVD, tumor invasion, lymph node metastasis, and survival in gastric cancer patients.

[An experimental serum pharmacological study on an application method in traditional Chinese medicine for treatment and prevention of asthma].

OBJECTIVE: To study the mechanism of herbal application along meridians for treatment and prevention of asthma by using serum pharmacological test to observe the effects of serum containing herbs against the constriction of tracheal spiral strips induced by acetylcholine chloride (Ach). METHODS: Guinea pigs were randomly divided into normal control group, normal saline (NS) application group, aminophylline application group, aminophylline injection group, 1-day herb application group, 7-day herb application group and 14-day herb application group. Asthma was induced by Hutson's method in guinea pigs except the normal control group. Guinea pigs in herb application groups were treated by external application of a compound herbal medicine 60 min once every day. Guinea pigs in NS application group were treated by external application of NS. Guinea pigs in the two aminophylline-treated groups were treated by external application and intraperitoneal injection of aminophylline at a dose of 400 mg/kg, respectively. The guinea pigs were killed and the sera were obtained after 1-day, 7-day and 14-day treatment in the three herb application groups, 7-day treatment in the NS application group, the aminophylline application and injection groups, respectively. Serum pharmacological method was used to do the experiment, the effects of different sera on the constriction of tracheal strips were observed, and the constriction rates were calculated. RESULT: The serum containing herbs had an effect in reducing the constriction of tracheal spiral strips induced by Ach, and the effect was similar to that of the serum obtained from the aminophylline injection group. The constriction rate of the tracheal spiral strips was decreased when herbal application treatment was prolonged within a period of time, and it became stable when herbal application treatment was between 7-14 days. The constriction of tracheal spiral strips induced by Ach could be reduced remarkably when it was previously treated by serum containing herbs. CONCLUSION: The anti-acetylcholine function with a time-dependent effect is one of the mechanisms of herbal application treatment along meridians for asthma, and furthermore, herbal application treatment along meridians might be useful for preventing asthma.

Effects of 5F from Pteris semipinnate L on growth of human pathological scars in nude mice / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of 5F from Pteris semipinnate L on the growth of human pathological scar in nude mice.</p><p><b>METHODS</b>5F from Pteris semipinnate L was administered at different doses in nude mouse models bearing human pathological scars. The morphology, histology, tumor growth factor-beta1 and type I collagen content of the scar tissues were examined after the administration.</p><p><b>RESULTS</b>Administration of 5F significantly reduced the volume of the implanted pathological scars in the nude mouse models, and histologically, the scar tissue exhibited a transition to the normal scar architecture with decreased TGF-beta1 and type I collagen content.</p><p><b>CONCLUSION</b>5F could effectively inhibit the growth of pathological scars in nude mice.</p>

Effects of adlay on azoxymethane-induced colon carcinogenesis in rats.

Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) is a grass crop used in traditional Chinese medicine and as a nutritious food. It has been reported that adlay has anti-inflammatory and anti-tumor activity. Cyclooxygenase-2 (COX-2) is an inducible enzyme functionally related to both inflammation and colon carcinogenesis and is the target of many chemopreventive agents. This study investigated the effect of adlay on colon carcinogenesis and COX-2 expression. In a short-term experiment, male F344 rats were fed diets containing different doses of dehulled adlay and received the colon-specific carcinogen, azoxymethane (AOM), by intraperitoneal injection. All rats were killed after 5 weeks of feeding, and the colons were examined for the preneoplastic lesion, aberrant crypt foci (ACF). Dietary dehulled adlay at levels of 10%, 20%, or 40% significantly reduced the numbers of ACF and aberrant crypts. Dehulled adlay reduced the number of ACF of different sizes but did not affect the crypt multiplicity. Most ACF were found in the middle and distal colons; dehulled adlay significantly suppressed the formation of ACF in the middle colon. In a long-term experiment, male F344 rats were fed diets containing different doses of dehulled adlay and injected with AOM. All rats were killed after 52 weeks of feeding, and colons were examined for tumors and COX-2 protein expression. The results indicated that dehulled adlay did not inhibit colon tumors in spite of a slight suppressing effect in the proximal colon. Rats fed diets containing 20% dehulled adlay had less COX-2 protein expression in both proximal and distal colon tumors. The inconsistent effects between COX-2 protein expression and tumor outcome may be due to regional differences in the colon and the malignancy of the tumors. These findings suggest that dehulled adlay suppresses early events in colon carcinogenesis but not the formation of tumors.

beta-Lapachone reduces endotoxin-induced macrophage activation and lung edema and mortality.

beta-Lapachone, a 1,2-naphthoquinone, is a novel chemotherapeutic agent. It has been shown to be capable of suppressing inducible nitric oxide synthase expression and function in rat alveolar macrophages. The authors further performed experiments to examine the molecular mechanism of beta-lapachone on LPS-induced responses in rat alveolar macrophages and to evaluate its in vivo antiinflammatory effect. A significant increase in nitrite production and inducible nitric oxide synthase expression was elicited in macrophages treated with LPS that was inhibited by coincubation with beta-lapachone. beta-Lapachone could also inhibit the production of tumor necrosis factor-alpha induced by LPS. LPS induces protein tyrosine phosphorylation and nuclear factor-kappaB binding activity by gel mobility shift assay in macrophages. These events were significantly inhibited by beta-lapachone. Furthermore, beta-lapachone in vivo protected against the induction of lung edema, lung-inducible nitric oxide synthase protein expression and nuclear factor-kappaB activation, lethality, and increased plasma nitrite and serum tumor necrosis factor-alpha levels induced by LPS. These results indicate that beta-lapachone suppresses inducible nitric oxide synthase induction and tumor necrosis factor-alpha production mediated by the inhibition of protein tyrosine phosphorylation and nuclear factor-kappaB activation caused by LPS. This results in a beneficial effect in an animal model of sepsis.