Dojuksan ameliorates tubulointerstitial fibrosis through irisin-mediated muscle-kidney crosstalk.

BACKGROUND: Sarcopenia progresses in chronic kidney disease (CKD) and is positively correlated with mortality in end-stage kidney disease patients. Circulating irisin, an exercise-induced myokine, gradually decreases during CKD stage progression. Irisin inhibits the progression of kidney fibrosis, which is the final common outcome of CKD. Our preliminary study with C2C12 cells showed that Dojuksan, a herbal decoction, increases the expression of PGC1α (a regulator of irisin) and FNDC5 (a precursor of irisin). HYPOTHESIS: Dojuksan may increase circulating irisin and prevent the progression of kidney fibrosis. STUDY DESIGN AND METHODS: Unilateral ureteral obstruction (UUO) was performed on seven-week-old male C57BL/6 mice to induce kidney tubulointerstitial fibrosis. Dojuksan (50, 100, or 200 mg/kg/day) or losartan (1.5 mg/kg/day), a standard clinical treatment for CKD, was administered orally one day prior to surgery and continued for seven days thereafter. To determine the role of irisin released from muscles, TGFß-stimulated murine proximal tubular epithelial cells (mProx24 cells) were treated with conditioned media (CM) from Dojuksan-treated C2C12 muscle cells transfected with FNDC5 siRNA. RESULTS: UUO mice exhibited muscle wasting along with progressive kidney injury. Similar to losartan, Dojuksan ameliorated kidney inflammation and fibrosis in UUO mice. Dojuksan, but not losartan, increased plasma irisin concentration in UUO mice. Dojuksan significantly increased basal FNDC5 expression and inhibited TNFα-induced and indoxyl sulfate-induced FNDC5 down-regulation in C2C12 cells. The TGFß-induced collagen I (COL1) up-regulation in mProx24 cells was effectively inhibited by CM from C2C12 cells after Dojuksan treatment. Moreover, irisin inhibited TGFß-induced COL1 in mProx24 cells, which was not affected by CM from C2C12 cells transfected with FNDC5 siRNA. CONCLUSION: Dojuksan ameliorates kidney fibrosis through irisin-mediated muscle-kidney crosstalk, suggesting that Dojuksan may be used as an alternative therapeutic agent against CKD.

Assessing the Anti-cancer Therapeutic Mechanism of a Herbal Combination for Breast Cancer on System-level by a Network Pharmacological Approach.

BACKGROUND/AIM: Accumulating evidence has shown therapeutic effects of herbals on breast cancer, a commonly diagnosed malignancy in women worldwide. However, their underlying mechanisms remain unclear. We aimed to explore the mode of action of a recently developed herbal combination at system-level. MATERIALS AND METHODS: We employed network pharmacological approaches to study the mechanism of a combination of three herbals, Astragalus membranaceus, Angelica gigas and Trichosanthes kirilowii by investigating active compounds and performing functional enrichment analysis for the interacting targets. RESULTS: For in silico pharmacokinetic evaluation, ten active ingredients interacted with fifty-six breast cancer-associated therapeutic targets. Functional enrichment analysis revealed that TNF, estrogen, PI3K-Akt and MAPK signaling pathways were involved in tumorigenesis and development of breast cancer. The pharmacological mechanisms might be associated with cellular effects on proliferation, cell cycle process and apoptosis. CONCLUSION: The present study provides novel insights into the system-level pharmacological mechanisms underlying a herbal combination used for breast cancer therapies.

Dual actions on gout flare and acute kidney injury along with enhanced renal transporter activities by Yokuininto, a Kampo medicine.

BACKGROUND: Prolonged hyperuricemia is associated with kidney disease or gouty arthritis. Whether Yokuininto, a commercially available Kampo medicine that has been used for osteoarthritis or rheumatoid arthritis, can exhibit anti-hyperuricemic and inflammatory effects remains elusive. In the present study, Yokuininto exerts multiple homeostatic action on serum uric acid (sUA) levels by blocking pro-inflammatory cytokine activities and inducing uricosuric function with anti-renal injury functions. METHODS: The sUA was measured in potassium oxonate (PO)-administered mice. Renal transporter uptake assays were performed using HEK293 cells overexpressing OAT1, OCT2 or OAT3, MDCKII cells overexpressing BCRP, and Xenopus oocytes overexpressing OAT3 or URAT1. Immunoblot and ELISA assays were performed to detect the molecules (OAT3, GLUT9, XO, NGAL, KIM-1 and IL-1α) in various human kidney cell lines. Cell viability analysis was performed to evaluate the cytotoxicity of Yokuininto [Ephedrine + pseudoephedrine 21.94%; Paeoniflorin 35.40% and Liquiritin 16.21% relatively measured by the ratios (HR-MS2 intensity / HR-MS1 intensity)]. RESULTS: Yokuininto (300 mg/kg) significantly reduced sUA by approximately 44% compared to that of PO-induced mice. The OAT3 levels were decreased in PO-induced hyperuricemic condition, whereas the GLUT9 transporter levels were markedly increased. However, PO did not alter the levels of URAT1. Yokuininto significantly inhibited the lipopolysaccharide (LPS)-induced secretion of IL-1α by approximately 63.2% compared to the LPS-treated macrophages. In addition, Yokuininto inhibited nitric oxide synthesis by approximately 33.7 (500 µg/mL) and 64.6% (1000 µg/mL), compared to that of LPS-treated macrophages. Yokuininto markedly increased xanthine oxidase inhibition activity. Furthermore, interleukin-1α (IL-1α), a pro-inflammatory cytokine, elevated neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) activities in LLC-PK1 cells. Expression of renal inflammatory biomarkers, NGAL and KIM-1, was reduced under the Yokuininto treatment by 36.9 and 72.1%, respectively. CONCLUSIONS: Those results suggest that Yokuininto may suppress inflammation and protect against kidney dysfunction in hyperuricemia. The present findings demonstrated that Yokuininto lowered sUA through both increased uric acid excretion and decreased uric acid production. Our results may provide a basis for the protection of prolonged hyperuricemia-associated kidney injury with uric acid-lowering agents such as Yokuininto.

Inhibitory effects of Kampo medicines, Keishibukuryogan and Shakuyakukanzoto, on the substrate uptake activities of solute carrier organic anion transporters.

The aim of this study was to assess the effects of Keishibukuryogan (K-06) and Shakuyakukanzoto (TJ-68), commercial herbal medicines, on the substrate uptake activities of renal organic anion transporters. We performed transporter uptake and cell viability assays in Xenopus oocytes and HEK293 human kidney embryonic cells treated with K-06 or TJ-68. K-06 and TJ-68 markedly inhibited the substrate uptake activities of URAT1, OAT1, and OAT3, while they did not exhibit non-cytotoxic effects. Our findings demonstrated that K-06 and TJ-68 inhibited the substrate uptake activities of renal transporters, suggesting their mechanism of action as nephroprotective agents.

Altered TNF-α response by Aconibal® and methotrexate in a lipopolysaccharide-induced setting of inflammatory conditions: Potential on a synergistic combination.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii (AC) is a common herbal medicine used as anti-inflammatory and analgesic agent in Eastern Asia. In Korea, a commercial processed AC (Aconibal®) is traditionally used to treat the symptoms of spondylosis deformans and rheumatic pain. AIM OF STUDY: Rheumatoid arthritis (RA) is systemic and autoimmune disease characterized by chronic inflammation. Methotrexate (MTX) is often the first-line therapy for RA. If MTX monotherapy is ineffective or RA is initially severe, adding a tumor necrosis factor alpha (TNF-α) inhibitor to the treatment can be beneficial. However, its inhibitory effects on RA when combined with MTX are unknown. Therefore, we investigated the stable modulation of and synergistic to additive effect on TNF-α using AC combined with MTX (AMC). MATERIALS AND METHODS: An inflammatory response mimicking RA was induced in the mouse macrophage cell line Raw 264.7 using interferon-γ or lipopolysaccharide (LPS). We predicted that AC and MTX at a 3:1 ratio would have synergistic therapeutic effects and this was determined using the Chou-Talalay method of median effect analysis and CalcuSyn software. We analyzed the profiles of various inflammatory cytokine-related proteins using Search tool for retrieval of interacting genes and Kyoto Encyclopedia of Genes and Genomes. RESULTS: The expression levels of selected inflammatory immune mediators such as interleukin (IL)-6, IL-1α, chemokine ligand 5, granulocyte-colony stimulating factor, nitric oxide synthase, and cyclooxygenase were reduced via regulation of the mitogen-activated protein kinase signaling pathway. AMC inhibited the levels of matrix metalloproteinases-1 and -3 in the human synovial cell line SW982. CONCLUSIONS: Our data show for the first time the potential beneficial effects of AMC in RA management.

Assessing the recovery from prerenal and renal acute kidney injury after treatment with single herbal medicine via activity of the biomarkers HMGB1, NGAL and KIM-1 in kidney proximal tubular cells treated by cisplatin with different doses and exposure times.

BACKGROUND: Acute kidney injury (AKI) is an initial factor in many kidney disorders. Pre- and intra-renal AKI biomarkers have recently been reported. Recovery from AKI by herbal medicine has rarely been reported. Thus, this study aimed to investigate the dose- and time-dependent effects of herbal medicines to protect against AKI in cisplatin-induced human kidney 2 (HK-2) cells by assessing the activities of high-mobility group box protein 1 (HMGB1), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1). METHODS: Proximal tubular HK-2 cell lines were treated with either 400 µM of cisplatin for 6 h or 10 µM of cisplatin for 24 h and then exposed to ten types of single herbal medicines, including Nelumbo nymphaea (NY) at a dose of 100 µg/mL. The AKI biomarkers HMGB1, NGAL and KIM-1 were repeatedly measured by an ELISA assay at 2, 4, and 6 h in the group treated with 400 µM of cisplatin to confirm necrotic cell death and at 6, 24, and 48 h in the group treated with 10 µM of cisplatin to examine apoptotic cell death. Recovery confirm was conducted through in vivo study using ICR mice for 3 day NY or Paeonia suffruticosa intake. RESULTS: Cisplatin treatment at a concentration of 10 µM decreased cell viability. Treatment with 400 µM of cisplatin reduced HMBG1 activity and resulted in lactate dehydrogenase release. In longer exposure durations (up to 48 h), NGAL and KIM-1 exhibited activity from 24 h onward. Additionally, NY treatment resulted in an approximately 50% change in all three biomarkers. The time-dependent profiles of HMGB1, NGAL and KIM-1 activities up to 48 h were notably different; HMGB1 exhibited a 7-fold change at 6 h, and NGAL and KIM-1 exhibited 1.7-fold changes at 24 h, respectively. Consistently, serum and urine NGAL and KIM-1 activities were all reduced in ICR mice. CONCLUSIONS: Several single herbal medicines, including NY, have a potential as effectors of AKI due to their ability to inhibit the activation of HMGB1, NGAL and KIM-1 in an in vitro AKI-mimicked condition and simple in vivo confirm. Furthermore, an in vivo proof-of-concept study is needed.

A systematic review of the pharmacokinetic and pharmacodynamic interactions of herbal medicine with warfarin.

OBJECTIVES: The aim of this study was to systematically review data regarding pharmacokinetic (PK)-pharmacodynamic (PD) parameters from randomized controlled trials relating to interactions between herbal medicines and warfarin. METHODS: Three electronic databases were searched to identify relevant trials. Two reviewers independently performed the study selection and data extraction. The risk of bias and reporting quality were also assessed independently by two reviewers using the Cochrane risk of bias tool and the consolidated standards of reporting trials (CONSORT). Outcomes were measured for all reported PK-PD parameters and adverse events. RESULTS: Nine randomized controlled trials met our inclusion criteria. Most of the included studies were unclear regarding the risk of bias and had a low quality of methodology. Using CONSORT, the reporting percentages for the articles ranged from 36.5% to 61.5% and the mean percentage for all articles was 45.6%. St John's wort and echinacea affected the PK parameters of warfarin. Ginseng, ginger, garlic, and cranberry had no significant effect on the PK parameters. American ginseng altered the PD parameters of warfarin. St John's wort, ginseng, Korea red ginseng, ginkgo, ginger, garlic, aged garlic, and echincea did not significantly alter the PD parameters. Studies of ginkgo and cranberry showed conflicting results on the PK parameters and PD parameters, respectively. The incidence of adverse events in all trials was low and no major adverse events were reported. CONCLUSIONS: It was difficult to determine whether ten herbal medicines had significant effects on the PK-PD parameters of warfarin. Low quality of evidence, different compounds within and different compositions of the herbs, and methodological limitations of the crossover study, which is a clinical study in which subjects receive a sequence of different interventions, made it difficult to form conclusions. Additional studies that remedy these vulnerabilities are necessary to verify these results.

A nationwide study of the incidence rate of herb-induced liver injury in Korea.

Discrepant incidence has been reported regarding the incidence of herb-induced liver injury (HILI). To address the growing worldwide concern of HILI, we evaluated the risk of HILI in a nationwide prospective study. Between April 2013 and January 2016, 1001 inpatients (360 males and 641 females) from 10 tertiary hospitals throughout South Korea were treated with herbal drugs and had their liver enzymes periodically measured. A total of six patients met the criteria for HILI with RUCAM scores ranging from 4 to 7. All these participants were women and developed the hepatocellular type of HILI. One HILI participant met the criteria for Hy's law; however, none of six cases presented clinical symptoms related to liver injury. This is the first nationwide prospective study that estimated the extent of the incidence of HILI [total: 0.60%, 95% confidence interval (CI) 0.12-1.08; women: 0.95%, 95% CI 0.19-1.68] and described its features in hospitalized participants.

A traditional Korean multiple herbal formulae (Yuk-Mi-Jihwang-Tang) attenuates acute restraint stress-induced brain tissue oxidation.

We aimed to evaluate the protective effects of Yuk-Mi-Jihwang-Tang (YJT) against acute restraint stress-induced brain oxidative damage. A water extract of YJT was prepared and subjected to high performance liquid chromatography - diode array detector-mass spectrometry (HPLC-DAD-MS). Thirty-six heads of C57BL/6J male mice (7 weeks) were divided into six groups (n = 6/group). The mice were orally administrated YJT (0, 50, 100, or 200 mg/kg) or vitamin C (100 mg/kg) for 5 consecutive days before 6 h of acute restraint stress. In the brain tissue, lipidperoxidation, antioxidant components, and pro-inflammatory cytokines were measured, and the serum corticosterone level was determined. Acute restraint stress-induced notably increased lipid peroxidation in brain tissues, and pretreatment with YJT showed a significant decreased the lipid peroxidation levels (p< 0.05). The levels of antioxidant components including total glutathione contents, activities of SOD and catalase were remarkably depleted by acute restraint stress, whereas these alterations were significantly restored by treatment with YJT (p< 0.05 or p< 0.01). The restraint stress markedly increased pro-inflammatory cytokines, such as TNF-α and IL-6 in the gene expression and protein levels (p< 0.05 or p< 0.01). Pretreatment with YJT significantly attenuated serum corticosterone (200 mg/kg, p < 0.05). YJT drastically attenuated the levels of 4- HNE, HO-1, Nox 2 and iNOSwhich were elevated during acute restraint stress, whereas the Nrf2 level was increased in brain tissue protein levels. Our data suggest that YJT protects the brain tissue against oxidative damage and regulates stress hormones.

Aconitum carmichaelii protects against acetaminophen-induced hepatotoxicity via B-cell lymphoma-2 protein-mediated inhibition of mitochondrial dysfunction.

We previously reported the clinical profile of processed Aconitum carmichaelii (AC, Aconibal(®)), which included inhibition of cytochrome P450 (CYP) 2E1 activity in healthy male adults. CYP2E1 is recognized as the enzyme that initiates the cascade of events leading to acetaminophen (APAP)-induced toxicity. However, no studies have characterized its role in APAP-induced hepatic injury. Here, we investigated the protective effects of AC on APAP-induced hepatotoxicity via mitochondrial dysfunction. AC (5-500 µg/mL) significantly inhibited APAP-induced reduction of glutathione. In addition, AC decreased mitochondrial membrane potential (Δψm) and B-cell lymphoma 2 (Bcl-2)-associated X protein levels (% change 46.63) in mitochondria. Moreover, it increased Bcl-2 (% change 55.39) and cytochrome C levels (% change 38.33) in mitochondria, measured using immunofluorescence or a commercial kit. Furthermore, cell membrane integrity was preserved and nuclear fragmentation inhibited by AC. These results demonstrate that AC protects hepatocytes against APAP-induced toxicity by inhibiting mitochondrial dysfunction.

In Vitro and in Vivo Neuroprotective Effects of Walnut (Juglandis Semen) in Models of Parkinson's Disease.

Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamines including dopamine (DA). MAO expression is elevated in Parkinson's disease (PD). An increase in MAO activity is closely related to age, and this may induce neuronal degeneration in the brain due to oxidative stress. MAO (and particularly monoamine oxidase B (MAO-B)) participates in the generation of reactive oxygen species (ROS), such as hydrogen peroxide that are toxic to dopaminergic cells and their surroundings. Although the polyphenol-rich aqueous walnut extract (JSE; an extract of Juglandis Semen) has been shown to have various beneficial bioactivities, no study has been dedicated to see if JSE is capable to protect dopaminergic neurons against neurotoxic insults in models of PD. In the present study we investigated the neuroprotective potential of JSE against 1-methyl-4-phenylpyridinium (MPP⁺)- or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicities in primary mesencephalic cells and in a mouse model of PD. Here we show that JSE treatment suppressed ROS and nitric oxide productions triggered by MPP⁺ in primary mesencephalic cells. JSE also inhibited depletion of striatal DA and its metabolites in vivo that resulted in significant improvement in PD-like movement impairment. Altogether our results indicate that JSE has neuroprotective effects in PD models and may have potential for the prevention or treatment of PD.

An experimental study on providing a scientific evidence for seven-time alcohol-steaming of Rhei Rhizoma when clinically used.

BACKGROUND: Rhei Rhizoma (RR) has been widely used as laxative and processed to alter its therapeutic actions or reduce its side effects. In this study, we evaluated experimentally the clinical application guideline that RR should be alcohol-steamed seven times before being used in elderly patients, as described in Dongeuibogam, the most famous book on Korean traditional medicine. METHODS: Unprocessed RR (RR-U) was soaked in rice wine, steamed and then fully dried (RR-P1). The process was repeated four (RR-P4) or seven times (RR-P7). Reversed-phase high-performance liquid chromatography was used to determine the RR-U, RR-P1, RR-P4 and RR-P7 (RRs) constituents. To evaluate the effect of RRs on liver toxicity, human hepatoma cells (HepG2) were treated with RRs at 100 µg/mL for 4 h and then cell viabilities were measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. To confirm the effects in vivo, 5-week-old male Sprague-Dawley rats were treated with RRs at 3 g/kg/day for 21 days. Body weight and serum biochemical parameters were measured and liver histology was assessed. RESULTS: The levels of sennosides decreased in processed RRs in an iteration-dependent manner, while the emodin level was unaffected. In HepG2 cells, cell viability was reduced with RR-U, while the toxicity decreased according to the number of processing cycles. The changes in body weight, relative liver weight and liver enzymes of RR-U-treated rats were reduced in processed RRs-treated rats. Histopathological analysis indicated swelling and cholestasis improved following seven times alcohol-steaming cycles. CONCLUSIONS: These results provide experimental evidence that RR-P7 almost completely reduces RR hepatotoxicity.

Potential benefits of acupuncture for enhanced recovery in gynaecological surgery.

We aimed to evaluate if acupuncture can improve clinical benefits and patient satisfaction after gynaecological surgery supported by enhanced recovery after surgery (ERAS) programmes. Therefore, we evaluated patient as well as clinical outcome in patient recovery after surgery. We searched MEDLINE, PubMed and EMBASE for articles dealing with post-operative acupuncture and extracted 9 suitable studies. We expected acupuncture to alleviate surgical stress, reduce emetic symptom and accelerate recovery from complications in pre-, intra-, and post-operative phases. Gastrointestinal motility and coldness achieved the full improvement rate of 50%. With regard to post-operative nausea and vomiting, 3 studies showed more than 30% and 1 showed 16% improvement. Sore throat and urinary retention achieved a mild improvement rate of 16% and 12%, respectively. In this study, we demonstrated that acupuncture can enhance recovery in gynaecological surgery without adverse effects and thus should be considered in ERAS.

Anticancer potential of an ethanol extract of Asiasari radix against HCT-116 human colon cancer cells in vitro.

Radix of Asiasarum heterotropoides var. mandshuricum F. Maekawa (A. radix) has been prescribed for treating pain, allergies and inflammatory disorders in traditional oriental medicine. However, only limited information on the anticancer effects of A. radix is currently available. The aim of this study was to determine the anticancer effect of the ethanol extract of A. radix (EEAR) on HCT-116 human colon cancer cells and to investigate its underlying mechanisms of action. EEAR significantly induced G2/M cell cycle arrest and apoptosis in HCT-116 cells. EEAR-induced apoptosis was observed in parallel with activation of caspases and an increased ratio of Bax (pro-apoptotic)/Bcl2 (anti-apoptotic). Western blot analyses revealed that EEAR elevated the expression of p53 and p21(Waf/Cip1) and decreased the expression of the regulator proteins of G2/M phase progression, such as cdc2 and cyclin B. The upregulation of p53 by EEAR was due to the increased levels of p53 mRNA without a similar increase in proteasome-mediated p53 degradation. EEAR-induced apoptosis in HCT-116 cells was dependent on p53 expression, as determined by siRNA-mediated p53 knockdown. Taken together, these results suggest that EEAR inhibits the growth of the HCT-116 cells through induction of G2/M cell cycle arrest and apoptosis, which are mediated by p53 expression.

Ethanol extract of Gleditsia sinensis thorn suppresses angiogenesis in vitro and in vivo.

BACKGROUND: Gleditsia sinensis thorns have been widely used in traditional Korean medicine for the treatment of several diseases, including obesity, thrombosis, and tumor-related diseases. The aim of the study is to determine the antiangiogenic effect of Gleditsia sinensis thorns in vitro and in vivo in a bid to evaluate its potential as an anticancer drug. METHODS: Ethanol extract of Gleditsia sinensis thorns (EEGS) were prepared and used for in vitro and in vivo assays. In vitro antiangiogenic effect of EEGS was determined in HUVEC primary cells by cell migration and tube formation assays. In vivo antiangiogenic effect of EEGS was determined by measuring vessel formation and vascular endothelial cells migrating into the implanted matrigels in nude mice. The angiogenesis-related proteins of which expression levels were altered by EEGS were identified by proteomic analysis. RESULTS: EEGS exerted a dose-dependent antiproliferative effect on HUVEC cells without significant cytotoxicity. Angiogenic properties, such as cell migration and tube formation, were significantly inhibited by EEGS in a dose-dependent manner. New vessel formation was also suppressed by EEGS, as determined by the directed in vivo angiogenesis assays in nude mice. EEGS reduced the expression of proangiogenic proteins, endothelin 1 and matrix metallopeptidase 2, in HUVEC cells. CONCLUSIONS: Our findings suggest that EEGS can inhibit angiogenesis by down-regulating proangiogenic proteins, and therefore it should be considered as a potential anticancer drug targeting tumor-derived angiogenesis.

Anti-proliferative neolignans from Saururus chinensis against human cancer cell lines.

Activity-guided fractionation of an 80% EtOH extract from the aerial parts of Saururus chinensis led to isolation of three anti-proliferative neolignans (1-3) along with four flavonoids (4-7) and four aristolactams (8-11). Their chemical structures were identified by analysis of spectroscopic data. All compounds 1-11 were evaluated for their activities against 28 human cancer cell lines using an in vitro cell proliferation assay. Compounds 1-3 showed potent anti-proliferative activities against cervical (C33a, IC50=0.01 µM for 1; 0.28 µM for 2; 2.80 µM for 3) and lung (NCI-H460, IC50=0.05 µM for 1; 1.37 µM for 2; 6.46 µM for 3) cancer cells without any remarkable cytotoxic effects on human normal lung cells as a control. Taken together, these data demonstrated the identification of anti-proliferative neolignans which are active components of S. chinensis.

Discovery of the inhibitors of tumor necrosis factor alpha with structure-based virtual screening.

Tumor necrosis factor alpha (TNF-α) has been considered as one of the attractive drug targets for allergic diseases including asthma. We have been able to identify five novel TNF-α inhibitors with a drug-design protocol involving the structure-based virtual screening and in vitro cell-based assay for antagonistic activity. Because the newly discovered inhibitors are structurally diverse and have the desirable physicochemical properties as a drug candidate, they deserve a further investigation as anti-asthmatic drugs. The interactions of the identified inhibitors in the binding site of TNF-α dimer are addressed in detail to understand the mechanisms for the stabilization of the inactive dimeric form of TNF-α.

Enhancing effect of HT008-1 on cognitive function and quality of life in cognitively declined healthy adults: a randomized, double-blind, placebo-controlled, trial.

HT008-1 is one of the most effective multiherb mixtures that have neuroprotective effects in traditional Korean medicine. The purpose of this study was to conduct a clinical trial of the efficacy of HT008-1 on the neuropsychological functioning and quality of life (QoL) in cognitively intact adults. One hundred and eighteen male (n - 42) and female (n = 76) volunteers who reported no history of dementia or significant neurocognitive impairments and obtained Korean Version of Mini Mental State Examination total scores of at least 24 were examined via an 8-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group, clinical trial. Participants were randomly assigned to receive either HT008-1 (n = 59) or placebo (n = 59) for 8 weeks. Efficacy measures consisted of participants' performance scores from pretreatment baseline to those obtained just before termination of treatment on standardized neuropsychological measures from the subsets of Wechsler Memory Scale-III (WMS-III). QoL was assessed by subjective questionnaires WHOQoL-Bref about five categories. Participants who scored in the lower third of the Auditory recognition delayed at baseline and received HT008-1 exhibited improvement on the WMS-III Auditory recognition delayed subtest compared with placebo controls. The HT008-1 group also improved on general health scores in the QoL test.