Kyung Hee University Korean Medicine Hospital

BACKGROUND: In a former meta-analysis review, acupuncture was considered a potentially effective treatment for dry eye syndrome (DES), but there were heterogeneities among the outcomes. We updated the meta-analysis and conducted subgroup analysis to reduce the heterogeneity and suggest the most effective acupuncture method based on clinical trials. METHODS: We searched for randomized controlled trials (RCTs) in 10 databases (MEDLINE, EMBASE, CENTAL, AMED, SCOPUS, CNKI, Wangfang database, Oriental Medicine Advanced Searching Integrated System (OASIS), Koreamed, J-stage) and searched by hand to compare the effects of acupuncture and artificial tears (AT). We also conducted subgroup analysis by (1) method of intervention (acupuncture only or acupuncture plus AT), (2) intervention frequency (less than 3 times a week or more than 3 times a week), (3) period of treatment (less than 4 weeks or more than 4 weeks), and (4) acupoints (BL1, BL2, ST1, ST2, TE23, Ex-HN5). The Bucher method was used for subgroup comparisons. RESULTS: Nineteen studies with 1126 patients were included. Significant improvements on the Schirmer test (weighted mean difference[WMD], 2.14; 95% confidence interval[CI], 0.93 to 3.34; p = 0.0005) and break up time (BUT) (WMD, 0.98; 95% CI, 0.79 to 1.18; p < 0.00001) were reported. In the subgroup analysis, acupuncture plus AT treatment had a weaker effect in BUT but a stronger effect on the Schirmer test and a better overall effect than acupuncture alone. For treatment duration, treatment longer than 1 month was more effective than shorter treatment. With regard to treatment frequency, treatment less than three times a week was more effective than more frequent treatment. In the acupoint analysis, acupuncture treatment including the BL2 and ST1 acupoints was less effective than treatment that did not include them. None of those factors reduced the heterogeneity. CONCLUSIONS: Acupuncture was more effective than AT in treating DES but showed high heterogeneity. Intervention differences did not influence the heterogeneity.

Primary dysmenorrhea, which is menstrual pain without pelvic pathology, is the most common gynecologic condition in women. Heat therapy has been used as a treatment. We assessed the evidence on heat therapy as a treatment for primary dysmenorrhea. We searched 11 databases for studies published through July 2018. All randomized controlled trials (RCTs) that addressed heat therapy for patients with primary dysmenorrhea were included. Data extraction and risk-of-bias assessments were performed by two independent reviewers. Risk of bias was assessed using the Cochrane risk-of-bias tool. Six RCTs met our inclusion criteria. Two RCTs found favorable effects of heat therapy on menstrual pain compared with unheated placebo therapy. Three RCTs found favorable effects of heating pads on menstrual pain compared with analgesic medication (n = 274; SMD -0.72; 95% confidence interval -0.97 to -0.48; P < 0.001; two studies). One RCT showed beneficial effects of heat therapy on menstrual pain compared with no treatment (n = 132; MD -4.04 VAS; 95% CI -4.88 to -3.20; P < 0.001). However, these results are based on relatively few trials with small sample sizes. Our review provided suggestive evidence of the effectiveness of heat therapy for primary dysmenorrhea, but rigorous high-quality trials are still needed to provide robust evidence.

Cervical cancer is the fourth most common cancer among women worldwide. Though several natural products have been reported regarding their efficacies against cervical cancer, there has been no review article that categorized them according to their anti-cancer mechanisms. In this study, anti-cancerous natural products against cervical cancer were collected using Pubmed (including Medline) and google scholar, published within three years. Their mechanisms were categorized as induction of apoptosis, inhibition of angiogenesis, inhibition of metastasis, reduction of resistance, and regulation of miRNAs. A total of 64 natural products suppressed cervical cancer. Among them, Penicillium sclerotiorum extracts from Cassia fistula L., ethanol extracts from Bauhinia variegate candida, thymoquinone obtained from Nigella sativa, lipid-soluble extracts of Pinellia pedatisecta Schott., and 1′S-1′-acetoxychavicol extracted from Alpinia conchigera have been shown to have multi-effects against cervical cancer. In conclusion, natural products could be attractive candidates for novel anti-cancer drugs.

STAT3 has been recognized as an efficacious drug target for prostate cancer because of its constitutive activation in this fatal disease. We recently identified the root bark of Morus alba Linn. as a potential STAT3 inhibitor among 33 phytomedicines traditionally used in Korea. Morusin, an active compound isolated from the root bark of Morus alba, has shown anti-oxidant and anti-inflammatory effects. In the present study, we examined whether morusin has a potential as an anti-cancer agent in prostate cancer. We found that morusin suppressed viability of prostate cancer cells, but little effect in normal human prostate epithelial cells. Morusin also reduced STAT3 activity by inhibiting its phosphorylation, nuclear accumulation, and DNA binding activity. In addition, morusin down-regulated expression of STAT3 target genes encoding Bcl-xL, Bcl-2, Survivin, c-Myc and Cyclin D1, which are involved in regulation of apoptosis and cell cycle. Furthermore, morusin induced apoptosis in human prostate cancer cells by reducing STAT3 activity. Taken together, these results suggest that morusin could be a potentially therapeutic agent for prostate cancer by reducing STAT3 activity and inducing apoptosis.

Sanguisorba officinalis Linne (S. officinalis, Rosaceae) has been used as a medicinal plant for the treatment of burns, hematemesis, melena, intestinal infections, and dermatitis for a long time in China, Korea, and Japan. The therapeutic efficacy of this herb is intimately associated with its anti-oxidant, anti-inflammatory, antiviral, antifungal, hemostatic, and anticancer activities. Its root contains triterpenoid saponins (zigyuglycoside I: C[Formula: see text]H[Formula: see text]O[Formula: see text] and ziyuglycoside II: C[Formula: see text]H[Formula: see text]O 8 ) and tannins (sanguiin H-6: C[Formula: see text]H[Formula: see text]O[Formula: see text]). It has been recently revealed that these active constituents of S. officinalis possess antiwrinkle properties without cytotoxicity. They also have anticancer effects by inducing apoptosis and cell cycle arrest. Moreover, they can inhibit proliferative tumorigenesis. The underlying mechanism involved in the pharmacological actions of these active constituents is mainly related to p38 MAPK signaling. Although various studies have reported its therapeutic activities and major chemical components, review articles that extensively organize various properties of S. officinalis and its major constituents are still scarce. Taken together, the objective of this paper is to provide overall pharmacological and phytochemical profiles of S. officinalis and its constituents (including ziyuglycoside I, ziyuglycoside II, and sanguiin H-6), and their potential roles in clinical applications for the treatment of inflammatory diseases, bleeding disorders, and cancer.

BACKGROUND: Natural products have increasingly attracted much attention as a valuable resource for the development of anticancer medicines due to the structural novelty and good bioavailability. This necessitates a comprehensive database for the natural products and the fractional extracts whose anticancer activities have been verified. DESCRIPTION: NPCARE (http://silver.sejong.ac.kr/npcare) is a publicly accessible online database of natural products and fractional extracts for cancer regulation. At NPCARE, one can explore 6578 natural compounds and 2566 fractional extracts isolated from 1952 distinct biological species including plants, marine organisms, fungi, and bacteria whose anticancer activities were validated with 1107 cell lines for 34 cancer types. Each entry in NPCARE is annotated with the cancer type, genus and species names of the biological resource, the cell line used for demonstrating the anticancer activity, PubChem ID, and a wealth of information about the target gene or protein. Besides the augmentation of plant entries up to 743 genus and 197 families, NPCARE is further enriched with the natural products and the fractional extracts of diverse non-traditional biological resources. CONCLUSIONS: NPCARE is anticipated to serve as a dominant gateway for the discovery of new anticancer medicines due to the inclusion of a large number of the fractional extracts as well as the natural compounds isolated from a variety of biological resources.

INTRODUCTION: This study aims to evaluate the efficacy and effectiveness of a mindfulness-based stress reduction (MBSR) program in improving sleep in cancer survivors. METHODS: Four electronic databases (Cochrane Library, EMBASE, PubMed, and PsycARTICLES) were searched for randomized controlled trials evaluating the effects of MBSR on the sleep of cancer survivors from their inception to May 2020. The primary outcome was sleep quality measured by validated questionnaires such as the Insomnia Severity Index and Pittsburgh Sleep Quality Index. The secondary outcomes were sleep parameters obtained from a sleep diary, polysomnography, and actigraphy. The included studies were critically appraised by the Cochrane risk of bias tool and meta-analyzed. RESULTS: = 58 %). However, there were no favorable results with sleep parameters. Compared to active controls, MBSR presented mixed results with sleep quality according to the outcomes and negative results with sleep parameters. CONCLUSION: This review suggests that MBSR helps cancer survivors improve sleep quality. Our results support the possibility of using MBSR for cancer survivors. However, its efficacy and effectiveness in improving sleep quality and sleep parameters are inconclusive because the number of included studies was few with inconsistent results. Further studies with high methodological quality are required to establish conclusive evidence about the efficacy and effectiveness of MBSR in improving sleep quality and sleep parameters in cancer survivors.

Context: Citrus unshiu Markovich (Rutaceae) peel is known to contain high concentrations of flavonoids and exerts pharmacological effects on antioxidant, anti-inflammation, allergies, diabetes and viral infections.Objective: Very little is known about potential activity of fermented dried Citrus unshiu peel extracts (FCU) using Bacillus subtilis, as well as its mechanism of action. We investigated the effects of FCU on the anti-inflammatory activities in murine macrophages and moisturizing effects in human keratinocytes.Materials and methods: We isolated the Bacillus subtilis from Cheonggukjang and FCU using these Bacillus subtilis to prepare samples. The cells were pre-treated with various extracts for 2 h and then induced with LPS for 22 h. We determined the NO assay, TNF-α, IL-6 and PGE2 in RAW 264.7 ells. The expression of SPT and Filaggrin by FCU treatment was measured in HaCaT cells.Result: We found that two types of FCU highly suppressed LPS-induced nitric oxide (NO) without exerting cytotoxic effects on RAW 264.7 cells (21.9 and 15.4% reduction). FCU inhibited the expression of LPS-induced iNOS and COX-2 proteins and their mRNAs in a concentration-dependent manner. TNF-α (59 and 30.9% reduction), IL-6 (39.1 and 65.6% reduction), and PGE2 secretion (78.6 and 82.5% reduction) were suppressed by FCU in LPS-stimulated macrophages. Furthermore, FCU can induce the production of hyaluronic acid (38 and 38.9% induction) and expression of Filaggrin and SPT in HaCaT keratinocyte cells.Discussion and conclusion: FCU potentially inhibits inflammation, improves skin moisturizing efficacy, and it may be a therapeutic candidate for the treatment of inflammation and dry skin.

BACKGROUND/AIMS: The use of tyrosine kinase inhibitors (TKIs) to target active epidermal growth factor receptor (EGFR)-harbouring mutations has been effective in patients with advanced non-small-cell lung cancer (NSCLC). However, the use of TKIs in NSCLS patients with somatic EGFR mutations, particularly T790M, causes drug resistance. Thus, in the present study, we investigated overcoming resistance against the TKI gefitinib by combination treatment with melatonin in H1975 NSCLC cells harbouring the T790M somatic mutation. METHODS: H1975 and HCC827 cells were treated with melatonin in combination with gefitinib, and cell viability, cell cycle progression, apoptosis, and EGFR, AKT, p38, Bcl-2, Bcl-xL, caspase 3 and Bad protein levels were examined. RESULTS: Treatment with melatonin dose-dependently decreased the viability of H1975 cells harbouring the T790M somatic mutation compared to HCC827 cells with an EGFR active mutation. Melatonin-mediated cell death resulted in decreased phosphorylation of EGFR and Akt, leading to attenuated expression of survival proteins, such as Bcl-2, Bcl-xL and survivin, and activated caspase 3 in H1975 cells, but not in HCC827 cells. However, we did not observe a significant change in expression of cell cycle proteins, such as cyclin D, cyclin A, p21 and CDK4 in H1975 cells. Surprisingly, co-treatment of gefitinib with melatonin effectively decreased the viability of H1975 cells, but not HCC827 cells. Moreover, co-treatment of H1975 cells caused consistent down-regulation of EGFR phosphorylation and induced apoptosis compared to treatment with gefitinib or melatonin alone. CONCLUSIONS: Our findings demonstrate that melatonin acts as a potent chemotherapeutic agent by sensitising to gefitinib TKI-resistant H1975 cells that harbour a EGFR T790M mutation.

L. (Moraceae) has previously demonstrated anticancer activity in various types of cancer cells such as hepatocellular carcinoma, glioma and prostate cancer. However, the effect of morusin on breast cancer cells remains unclear. In the present study, the potential of morusin as an anti-cancer agent in breast cancer was investigated. The results of the present study revealed that the treatment of morusin induced cell death in various human breast cancer cell lines, but exhibited little effect on normal human breast epithelial cells. In Annexin V-propidium iodide double staining assays, morusin significantly increased apoptosis in a dose-dependent manner in human breast cancer cells. The apoptosis marker proteins cleaved caspase 3 and 9 were consistently upregulated following treatment of cells with morusin in a time- and dose-dependent manner. Furthermore, morusin was demonstrated to modulate the expression of the anti-apoptotic protein Survivin and pro-apoptotic protein B-cell lymphoma 2-associated-x protein (Bax) in human breast cancer cells. These results indicate that morusin induces apoptosis by suppressing Survivin and inducing Bax proteins, suggesting that morusin is a potentially effective therapeutic agent for the treatment of patients with breast cancer.

Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty-five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine-type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.

OBJECTIVES: To analyze the efficacy and safety of auricular acupuncture (AA) in patients with cognitive impairment and dementia. METHODS: Twelve electronic databases were searched for randomized controlled trials evaluating effects of AA in patients with cognitive impairment and/or dementia, from their inception to August 2017. The primary outcome was cognitive function, and secondary outcomes were self-care ability, quality of life, clinical efficacy rate, and incidences of adverse events. RESULTS: Nine studies were included, and five involving 677 participants were analyzed quantitatively. Compared with Western medications (WM), AA had mixed effects on cognitive functions (Mini-Mental State Examination [MMSE], mean difference [MD] 0.73, 95% confidence interval [CI] -0.02 to 1.48; Hierarchic Dementia Scale [HDS], MD 2.21, 95% CI 1.09 to 3.33); there was no significant improvement in the activities of daily living (ADL) score (MD 0.20, 95% CI -3.51 to 3.91) in patients with vascular dementia (VD). Compared to WM, AA combined with WM showed better clinical efficacy rate (risk ratio [RR] 1.42, 95% CI 1.06 to 1.91) in patients with VD; there was no significant improvement in cognitive functions (MMSE, MD 0.97, 95% CI -0.44 to 2.38; Montreal Cognitive Assessment [MoCA], MD 0.22, 95% CI -1.83 to 2.27) in patients with mild cognitive impairment (MCI). Compared to herbal medicine (HM), AA plus HM showed significant improvements in cognitive function (MMSE, MD 1.31, 95% CI 0.13 to 2.49) in patients with MCI and patients with vascular cognitive impairment, no dementia (VCIND) and in ADL score (MD -6.70, 95% CI -8.78 to -4.62) in patients with MCI. No adverse event associated with AA was reported. CONCLUSION: The evidence reveals mixed efficacy of AA in patients with cognitive impairment and/or dementia. However, the results were inconclusive because of the small number and poor methodological quality of the included studies.

BACKGROUND: Although alopecia affects the quality of life, its pathogenesis is unknown, because cellular interactions in the hair follicle are complex. Several authors have suggested using herbal medicine to treat alopecia, and bioinformatics and network pharmacology may constitute a new research strategy in this regard because herbal medicines contain various chemical components. This study used association rule mining (ARM) and network analysis to analyze the combinations of medicinal herbs used to treat alopecia. METHODS: We searched Chinese, Korean, and English databases for literature about alopecia treatment, extracting the names of each herbal prescription and herb. The meridian tropism and classification category of each herb were also investigated. Using ARM, we identified frequently combined two-herb and three-herb sets. Using network analysis, we divided the herbs into several modules according to prescription pattern. RESULTS: Fifty-six articles and 489 herbal medicines were included-312 internal and 177 external medicines. Among the 312 medicinal herbs used in internal medicine group, the most frequently combined two-herb set was Polygonum multiflorum Thunb. () and Angelica sinensis (Oliv.) Dlels (). The most frequently used three-herb combination was Polygonum multiflorum Thunb., Angelica sinensis (Oliv.) Dlels, and Ligusticum chuanxiong Hort. (). In network analysis, three modules were identified. The herbs of Module 1 were related to the liver and kidney meridians, and those of Module 3 were related to the Stomach meridian. CONCLUSIONS: We identified the frequency, characteristics, and functional modules of herb combinations frequently used in alopecia treatment. We confirmed the value of classical medicinal herb theory. This finding will prompt further bioinformatics and network pharmacology research on alopecia.

Alterations in mitochondrial respiration contribute to the development and progression of cancer via abnormal biogenesis, including generation of reactive oxygen species. Ubiquinol-cytochrome c reductase hinge protein (UQCRH) consists of the cytochrome bc1 complex serving respiration in mitochondria. In the present study, we analyzed UQCRH abnormalities in hepatocellular carcinoma (HCC) and its association with clinical outcomes of patients. UQCRH expression in HCC was determined via semiquantitative and quantitative real-time reverse transcriptase polymerase chain reaction of 96 surgically resected HCC tissues positive for hepatitis B virus surface antigen. UQCRH was frequently overexpressed in HCC tissues (46.8%, based on 2.1-fold cutoff). UQCRH overexpression was observed in HCCs with larger tumor size, poorer differentiation, or vascular invasion. Kaplan-Meier analysis revealed significantly shorter overall (P = 0.005) and recurrence-free survival (P = 0.027) in patients with tumors overexpressing UQCRH. The prognostic impact of UQCRH was significant in subgroups of patients divided according to the α-fetoprotein (AFP) level. The patient subgroup with higher AFP levels (≥20 ng/mL) exhibited significant differences in 5-year overall (18.5% vs. 67.9%) and recurrence-free survival rates (11.1% vs. 46.4%) between groups with and without UQCRH overexpression. In contrast, no marked survival differences were observed between subgroups with lower AFP levels (<20 ng/mL). Multivariate analysis defined UQCRH as an independent poor prognostic factor. Conclusively, our results indicate that UQCRH overexpression is correlated with poor outcomes of HCC patients. Furthermore, in patients grouped as high risk based on elevated AFP, lack of UQCRH overexpression could be a useful indicator for clinical treatment.

-β-D-galactopyranosyl, is a well-known flavonol glycoside that is abundant in various fruits, vegetables, and medicinal plants. Hyp has been suggested to exhibit a wide range of biological actions, including cardiovascular, renal, neuroprotective, antifungal, antifibrotic, and anticancer effects. Accumulating evidence supports the pharmacological activities of Hyp in improving liver pathophysiology. Hence, the present literature review aims to summarize preclinical data suggesting the beneficial effects and underlying mechanisms of Hyp. In addition, our study focuses on hepatic antioxidant defense signaling to assess the underlying mechanisms of the biological actions of Hyp that are closely associated with liver diseases. Experimental findings from an up-to-date search showed that Hyp possesses hepatoprotective, antiviral, antisteatotic, anti-inflammatory, antifibrotic, and anticancer activities in cellular and animal models related to liver dysfunction by enhancing antioxidant responses. In particular, hepatocellular antioxidant defense via activation of erythroid-related nuclear factor 2 by Hyp chiefly explains how this compound acts as a therapeutic agent in liver diseases. Thus, this review emphasizes the therapeutic potential of Hyp as a strong antioxidative substance that plays a crucial role in the regulation of various liver disorders during their pathogenesis.

The coronavirus disease 2019 (COVID-19) pandemic affected the world, and its deleterious effects on human domestic life, society, economics, and especially on human mental health are expected to continue. Mental health experts highlighted health issues this pandemic may cause, such as depression, anxiety, obsessive compulsive disorder, and post-traumatic stress disorder. Mind-body intervention, such as mindfulness meditation, has accumulated sufficient empirical evidence supporting the efficacy in improving human mental health states and the use for this purpose has been increasing. Notably, some of these interventions have already been tried in the form of telemedicine or eHealth. Korea, located adjacent to China, was exposed to COVID-19 from a relatively early stage, and today it is evaluated to have been successful in controlling this disease. "The COVID-19 telemedicine center of Korean medicine" has treated more than 20% of the confirmed COVID-19 patients in Korea with telemedicine since 9 March 2020. The center used telemedicine and mind-body modalities (including mindfulness meditation) to improve the mental health of patients diagnosed with COVID-19. In this paper, the telemedicine manual is introduced to provide insights into the development of mental health interventions for COVID-19 and other large-scale disasters in the upcoming new-normal era.

BACKGROUND: The incidence of inflammatory bowel disease (IBD), an inflammatory disorder of the gastrointestinal system has increased. IBD, characterized by aberrant immune responses against antigens, is thought to be caused by the invasion of enterobacteria. The pathogenesis of IBD is complicated, hence novel effective therapeutic agents are warranted. Therefore, this study evaluates the potential of Artemisia argyi, a medicinal herb, in alleviating IBD. METHODS: The effectiveness of the A. argyi ethanol extract was verified both in vitro and in vivo. Inflammation was induced in RAW 264.7 cells by 1 μg/mL of lipopolysaccharide (LPS) and by 3% dextran sodium sulfate (DSS) in a DSS-induced colitis mouse model. During the ten-day colitis induction, 200 mg/kg of A. argyi ethanol extract was orally administered to the treatment group. Levels of inflammation-related proteins and genes were analyzed in the colon, serum, and lymphoid tissues, i.e., Peyer's patches (PPs) and spleen. The chemical constituent of the A. argyi ethanol extract was identified using an ultra-high performance liquid chromatography mass spectrometry (UPLC-MS/MS) analysis. RESULTS: A. argyi ethanol extract treatment ameliorated IBD symptoms and reduced the expression of inflammation-related proteins and genes in the colon and serum samples. Furthermore, A. argyi treatment induced the activation of anti-oxidative associated proteins, such as nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1); and the treatment have also inhibited nuclear factor-κB (NF-κB), a central mediator of inflammatory responses. A. argyi enhanced the immunomodulatory effects in the PPs and spleen, which may stem from interleukin-10 (IL-10) upregulation. Chemical analysis identified a total of 28 chemical compounds, several of which have been reported to exert anti-inflammatory effects. CONCLUSIONS: The effectiveness of the A. argyi ethanol extract in alleviating IBD was demonstrated; application of the extract successfully mitigated IBD symptoms, and enhanced immunomodulatory responses in lymphoid tissues. These findings suggest A. argyi as a promising herbal medicine for IBD treatment.

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promised anticancer medicine targeting only the tumor, most cancers show resistance to TRAIL-induced apoptosis. For this reason, new therapeutic strategies to overcome the TRAIL resistance are required for more effective tumor treatment. In the present study, potential of tanshinone IIA as a TRAIL sensitizer was evaluated in human non-small cell lung cancer (NSCLC) cells. NSCLC cells showed resistance to TRAIL-mediated cell death, but combination treatment of Tanshinone IIA and TRAIL synergistically decreased cell viability and increased apoptosis in TRAIL-resistant NSCLC cells. Tanshinone IIA greatly induced death receptor 5 (DR5), but not death receptor 4 (DR4). Furthermore, DR5 knockdown attenuated the combination treatment of tanshinone IIA with TRAIL-mediated cell death in human NSCLC cells. Tanshinone IIA also increased CHOP and activated the PERK-ATF4 pathway suggesting that tanshinone IIA increased DR5 and CHOP by activating the PERK-ATF4 pathway. Tanshinone IIA also downregulated phosphorylation of STAT3 and expression of survivin. Taken together, these results indicate that tanshinone IIA increases TRAIL-induced cell death via upregulating DR5 and downregulating survivin mediated by, respectively, selective activation of PERK/ATF4 and inhibition of STAT3, suggesting combinatorial intervention of tanshinone IIA and TRAIL as a new therapeutic strategy for human NSCLC.

(hawthorn), a flowering shrub or tree, is a member of the Rosaceae family and consists of approximately 280 species that have been primarily cultivated in East Asia, North America, and Europe. Consumption of hawthorn preparations has been chiefly associated with pharmacological benefits for cardiovascular diseases, including congestive heart failure and angina pectoris. Treatment with hawthorn extracts can be related to improvements in the complex pathogenesis of various hepatic and cardiovascular disorders. In this regard, the present review described that the presence of hawthorn extracts ameliorated hepatic injury, lipid accumulation, inflammation, fibrosis, and cancer in an abundance of experimental models. Hawthorn extracts might have these promising activities, largely by enhancing the hepatic antioxidant system. In addition, several mechanisms, including AMP-activated protein kinase (AMPK) signaling and apoptosis, are responsible for the role of hawthorn extracts in repairing the dysfunction of injured hepatocytes. Specifically, hawthorn possesses a wide range of biological actions relevant to the treatment of toxic hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Accordingly, hawthorn extracts can be developed as a major source of therapeutic agents for liver diseases.

In spite of billions of dollars spent on cancer research each year, overall cancer incidence and cancer survival has not changed significantly in the last half century. Instead, the recent projection from the World Health Organization suggests that global cancer incidence and death is expected to double within the next decade. This requires an "out of the box" thinking approach. While traditional medicine used for thousands of years is safe and affordable, its efficacy and mechanism of action are not fully reported. Demonstrating that traditional medicine is efficacious and how it works can provide a "bed to bench" and "bench to bed" back approach toward prevention and treatment of cancer. This current review is an attempt to describe the contributions of traditional Korean medicine (TKM) to modern medicine and, in particular, cancer treatment. TKM suggests that cancer is an outcome of an imbalance of body, mind, and spirit; thus, it requires a multimodal treatment approach that involves lifestyle modification, herbal prescription, acupuncture, moxibustion, traditional exercise, and meditation to restore the balance. Old wisdoms in combination with modern science can find a new way to deal with the "emperor of all maladies."