Efficacy and safety of Onkyeong-tang in treating cold hypersensitivity in the feet of Korean women: protocol for a double-blind, randomized, placebo-controlled, parallel-group, multicenter clinical study.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) commonly affects Asian women, especially Korean women, and it negatively impacts the quality of life of the affected individuals. One commonly used herbal prescription for treating CHHF is Onkyeong-tang (OKT). Although OKT is widely used clinically in treating CHHF, no randomized clinical trial has been performed to evaluate the efficacy and safety of OKT in the treatment of cold hypersensitivity in the feet (CHF). This clinical trial aims to provide objective evidence for the basis of using OKT in the treatment of CHF in Korean women. METHODS: This trial will be a double-blind, randomized, placebo-controlled, parallel-group, multicenter pilot study. A total of 112 participants will be randomly divided into an OKT treatment group or a placebo group with a 1:1 ratio via a web-based randomization system. The OKT and placebo groups will receive prescribed medications orally three times per day (3 g each time) before or between meals for 8 weeks. The primary outcome studied will be the changes in Visual Analog Scale (VAS) scores of CHF from baseline. Secondary outcomes studied will be the VAS score changes of cold hypersensitivity in the hands, changes in the skin temperature of the hands and feet, total scores of the Korean version of the World Health Organization Quality of Life Scale-abbreviated version, and the results of the cold stress test. DISCUSSION: This trial will be the first clinical trial to assess the efficacy and safety of OKT in the treatment of CHF. We anticipate that the findings of the study will provide evidence for the basis of using OKT in treating CHF symptoms and generate basic data for designing a further large-scale randomized clinical trial. TRIAL REGISTRATION: Clinical Research Information Service (CRIS): KCT0003723. Retrospectively registered on 8 April 2019.

Anti-inflammatory effect of Acalypha australis L. via suppression of NF-κB signaling in LPS-stimulated RAW 264.7 macrophages and LPS-induced septic mice.

We evaluated the anti-inflammatory activity of methanol extracts of Chinese medicinal plants from Beijing and determined which extract was the most effective. We found the methanol extract of Acalypha australis L. (AAL) to be the most effective. AAL has been used for clearing heat, toxic material, and hemostasia in Chinese medicine. Although these uses are closely related to inflammation, the anti-inflammatory effect of AAL has not yet been described and its underlying mechanism remains unclear. Therefore, we aimed to identify anti-inflammatory effect of AAL and its underlying mechanism in vitro and in vivo. In RAW 264.7 macrophages, cytotoxicity was evaluated by MTT assay and nitric oxide (NO) was measured with Griess reagent. To confirm the production of pro-inflammatory cytokines and its mRNA expression, enzyme immunoassay (EIA) and quantitative real-time PCR (qRT-PCR) were performed. Further, protein expression was analyzed by western blotting. Septic shock was induced by intraperitoneal injection of LPS (25 mg/kg) in mice. One hour before LPS injection, AAL (25 and 50 mg/kg) was administered orally. In LPS-stimulated macrophages, AAL inhibited NO production at concentrations without cytotoxicity. Additionally, AAL reduced not only inducible nitric oxide synthase (iNOS) expression but the production of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by attenuating nuclear factor-kappa B (NF-κB)-related proteins (NF-κB p65, phosphorylation of inhibitor κB-α; p-IκB-α, phosphorylation of inhibitor κB kinase-α/ß; p-Ikk-α/ß). Moreover, AAL enhanced the survival rate of mice through the inhibition of iNOS expression and IL-6 and interleukin-1ß (IL-1ß) production in LPS-induced septic mice. Furthermore, AAL also reduced the expression of NF-κB-related proteins. These finding suggest that AAL is related to the modulation of inflammatory reactions by blocking NF-κB activation in LPS-stimulated RAW 264.7 macrophages and LPS-induced septic mice.

Antiphotoaging Potential of Extracts of Yin-Tonic Herbal Medicine in Skin Cell and Human Skin Equivalent.

Yin-tonic herbal medicines have been shown to possess properties that make skin healthy by nourishing within various organs of the body. However, the antiphotoaging effect of these medicines on the skin has not been fully studied. Photoaging occurs with prolonged sun exposure and causes skin damage and aging, with depletion of the dermal extracellular matrix and chronic alterations in skin structure, such as wrinkles. In this study, we assessed the antiphotoaging effects of eight yin-tonic herbal medicines on human skin cells and skin equivalents. The levels of type I procollagen and matrix metalloproteinase-1 (MMP-1) in ultraviolet B- (UVB-) irradiated CCD-986sk fibroblasts were measured, and then three medicines were chosen based on screening results. Using UVB-irradiated human skin equivalents, we evaluated the effect of three yin-tonic herbal medicines on histological changes of skin, epidermal and dermal thickness, and MMP-1 production. Furthermore, we observed collagen fiber content and protein expression of filaggrin in UVB-irradiated human skin equivalents. Yin-tonic herbal medicines increased type I procollagen levels and decreased the production of MMP-1 in UVB-irradiated CCD-986sk fibroblasts. The three selected yin-tonic herbal medicines recovered the collagen content and filaggrin expression via MMP-1 downregulation in UVB-irradiated human skin equivalents. Our results show that yin-tonic herbal medicines can prevent skin photoaging by reduction of MMP-1 levels and increasing the expression of moisturizing factors. Based on these results, we suggest that yin-tonic herbal medicines have the potential to be used as helpful agent for skin photoaging.

The efficacy and safety of Sipjeondaebo-tang in Korean patients with cold hypersensitivity in the hands and feet: a protocol for a pilot, randomized, double-blind, placebo-controlled, parallel-group clinical trial.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) is frequent in Asian countries including Korea. The quality of life can be degraded by the symptoms of CHHF. In particular, gynecological disorders such as menstrual pain, infertility, leucorrhea, and irregular bleeding may be related to CHHF. Sipjeondaebo-tang (SDT) is widely used in the treatment of various diseases including CHHF by balancing Yin and Yang, restoring the deterioration of physiological function, and improving immunity. However, the efficacy of SDT in the treatment of CHHF has not been assessed in clinical trials. Therefore, we aimed to investigate the feasibility of a full randomized clinical trial of SDT for the treatment of CHHF in Korean women through this trial. METHODS: This study will be a pilot, randomized, double-blind, two-arm, placebo-controlled, parallel-group, multicenter clinical trial. Women aged 19-59 years who present with CHHF will be recruited from five university hospitals. A total of 60 subjects will be randomly assigned to a treatment group (SDT) or a placebo group at a 1:1 ratio. The subjects will receive 3 g of either SDT or placebo three times daily for 8 weeks. The primary outcome measures will be the Visual Analogue Scale scores of CHHF. The secondary outcome measures will be changes in body temperature in both the hands and the feet as measured using a thermometer and the Korean version of the World Health Organization Quality of Life Scale Abbreviated Version. DISCUSSION: This will be the first trial to investigate the efficacy and safety of SDT in the treatment of CHHF. This study will provide basic clinical information regarding Korean herbal medicine treatment of CHHF and a clinical basis for designing a full randomized clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374345 . Registered on 15 February 2018.

Efficacy and safety of Ojeok-san in Korean female patients with cold hypersensitivity in the hands and feet: study protocol for a randomized, double-blinded, placebo-controlled, multicenter pilot study.

BACKGROUND: This study aims to evaluate the safety, efficacy, and feasibility of a full randomized clinical trial of Ojeok-san in Korean female patients with cold hypersensitivity in the hands and feet. METHODS: This study is a multicenter, double-blinded, randomized, placebo-controlled, two-arm, parallel-group pilot clinical trial. A total of 60 participants will be enrolled and randomly assigned to the Ojeok-san treatment group or the placebo control group, in a 1:1 ratio using an Internet-based randomization system. Each group will be administered Ojeok-san or placebo three times per day for 8 weeks. The primary outcome will be the mean change in the Visual Analog Scale scores of cold hypersensitivity in the hands from baseline to week 8. Secondary outcomes will include the mean changes in the skin temperature of the extremities, recovery rate of the skin temperature of hands after cold stress test, and the score of Korean version of the WHO Quality of Life Scale abbreviated version. DISCUSSION: The findings of this study should provide meaningful information for a further large-scale, randomized controlled trial to confirm the safety and efficacy of Ojeok-san on cold hypersensitivity in the hands and feet in female patients. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03083522 . Registered on 20 March 2017.

Inhibitory Effects of Helianthus tuberosus Ethanol Extract on Dermatophagoides farina body-induced Atopic Dermatitis Mouse Model and Human Keratinocytes.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex symptoms. To treat AD without adverse effects, alternative therapeutic agents are required. The tubers of Helianthus tuberosus L. (Jerusalem artichoke) have been used in folk remedies for diabetes and rheumatism. However, its effect on AD development remains unknown. Therefore, this study examined the inhibitory effect of H. tuberosus (HT) on AD skin symptoms using an NC/Nga mouse model and HaCaT keratinocytes. The effect of HT and associated molecular mechanisms were evaluated in Dermatophagoides farina body (Dfb)-induced AD mice and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes by ELISA, western blot, and histological analysis. Topical HT administration attenuated AD skin symptoms in Dfb-induced AD mice, with a significant reduction in the dermatitis score and production of inflammatory mediators. HT also decreased epidermal thickness and mast cell infiltration. Moreover, HT restored filaggrin expression and inhibited adhesion molecules in the mice. These effects were confirmed in vitro. Furthermore, HT suppressed the activation of NF-κB, Akt, and mitogen-activated protein kinase (MAPK) signaling pathways induced by TNF-α/IFN-γ. These results suggest that HT is a potential therapeutic agent or supplement for skin allergic inflammatory diseases such as AD.