New fusidane-type nortriterpenoids from the Arctic marine-derived fungus Simplicillium lamellicola culture medium with their inhibitory effect on benign prostatic hyperplasia.

Three new fusidane-type nortriterpenoids, simplifusinolide A, 24-epi simplifusinolide A, and simplifusidic acid L (1-3), were isolated from the EtOAc extract of the Arctic marine-derived fungus Simplicillium lamellicola culture medium, together with fusidic acid (4) and 16-O-deacetylfusicid acid (5). The structures of the isolated compounds were elucidated by NMR and MS analyses. The absolute configurations of compounds 1-3 were established by the quantum mechanical calculations of electronic circular dichroism and gauge-including atomic orbital NMR chemical shifts, followed by DP4 + analysis. Benign prostatic hyperplasia (BPH) is a major urological disorder in men worldwide. The anti-BPH potentials of the isolated compounds were evaluated using BPH-1 and WPMY-1 cells. Treatment with simplifusidic acid L (3) and fusidic acid (4) significantly downregulated the mRNA levels of the androgen receptor (AR) and its downstream effectors, inhibiting the proliferation of BPH-1 cells. Specifically, treatment with 24-epi simplifusinolide A (2) significantly suppressed the cell proliferation of both BPH-1 and DHT-stimulated WPMY-1 cells by inhibiting AR signaling. These results suggest the potential of 24-epi simplifusinolide A (2), simplifusidic acid L (3) and fusidic acid (4) as alternative agents for BPH treatment by targeting AR signaling.

Effects of Magnoliae Flos on Atopic Dermatitis-Like Inflammation Evaluated via Extracellular Signal-regulated Kinase or Signal Transducers and Activators of Transcription 1/3 Signalling Pathways.

Atopic dermatitis is a chronic inflammatory skin  disease. Skin is the largest organ and plays a pivotal role in protecting the body. Not only does the skin act as a physical barrier against the external environment, but it also has its own immune system. Atopic dermatitis is caused by prolonged excessive inflammatory responses that worsen under imbalanced cutaneous immune system skin conditions. Although the prevalence and burden of atopic dermatitis is increasing, the standard therapeutic agents remain unclear due to  the complicated pathophysiology of the condition. The objective of this study is to examine the use of Magnoliae flos, the dried flower bud of Magnolia biondii or  related plants. The effects and underlying mechanism of  action of aqueous extract of the buds of Magnoliae flos (MF) were evaluated. Immortalized human keratinocytes (HaCaT) stimulated with tumour necrosis factor-α and interferon-γ mixture and NC/Nga mice stimulated with 2,4-dinitrochlorobenzene were used as atopic dermatitis models, in vitro and in vivo, respectively. The effects of MF were determined by measuring the suppression of pro-inflammatory signalling pathways, such as extracellular signal-regulated kinase or signal transducers and activators of transcription 1/3 and restoring skin barrier molecules. In conclusion, MF is a potential therapeutic alternative for the treatment of atopic dermatitis through repressing inflammatory pathways.

Apocynin alleviates weight gain and obesity-induced adipose tissue inflammation in high-fat diet-fed C57BL/6 mice.

Obesity involves chronic low-grade inflammation within adipose tissue. Apocynin (APO) is a therapeutic agent for the treatment of inflammatory diseases. Therefore, the present study aimed to investigate whether APO can reduce weight gain and obesity-induced adipose tissue inflammation. C57BL/6 mice were administered APO or orlistat (Orli) as a positive control with a high-fat diet (HFD) for 12 weeks. Lipopolysaccharide-stimulated 3T3-L1 adipocytes were used for the in vitro study. Our results showed a significantly lower white adipose tissue (WAT) mass index in 10 mg/kg APO-treated mice than in 20 mg/kg Orli-treated mice. Moreover, the protein expression of adipose triglyceride lipase, fatty acid synthase, sterol regulatory element-binding transcription factor 1, and peroxisome proliferator-activated receptor γ was reversed in the WAT of 10 mg/kg APO-treated mice. Furthermore, APO reduced the expression of the macrophage marker F4/80, decreased the mRNA levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, and increased the mRNA levels of interleukin-10 in WAT. APO decreased the phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p65 in vivo and in vitro. Notably, APO had a stronger effect on the amelioration of adipose tissue inflammation than Orli did. Our findings lay the foundation for research on the use of APO as an agent to ameliorate weight gain and obesity-induced inflammatory diseases.

Magnoliae flos Downregulated Lipopolysaccharide-Induced Inflammatory Responses via NF-κB/ERK-JNK MAPK/STAT3 Pathways.

Background: Magnoliae flos is the dried flower bud of Magnolia biondii and related plants. It has been used as a medicinal herb for the treatment of rhinitis, sinusitis, and sinus headaches. Nevertheless, the effects of Magnoliae flos in microbial infection or sepsis remain unclear. In this study, we investigated the anti-inflammatory effects of Magnoliae flos water extract (MF) in lipopolysaccharide- (LPS-) induced septic mice and LPS-stimulated RAW264.7 macrophages. Results: We found that MF reduced the mortality of LPS-challenged mice. Enzyme immunoassays and reverse transcription polymerase chain reaction analysis revealed that MF administration attenuated mRNA expression and protein production of proinflammatory mediators, including cyclooxygenase 2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. In parallel to these results in mice, pretreatment with MF suppressed the LPS-induced production of proinflammatory mediators in RAW264.7 macrophages. In addition, we found that MF exerted its suppressive effects by inhibiting the activation of the mitogen-activated protein kinase, nuclear factor-κB, and signal transducer and activator of transcription pathways at the protein level. Conclusion: MF could be a potential therapeutic agent for regulating excessive inflammatory responses in sepsis.

Umbelliferone Ameliorates Benign Prostatic Hyperplasia by Inhibiting Cell Proliferation and G1/S Phase Cell Cycle Progression through Regulation of STAT3/E2F1 Axis.

Umbelliferone (UMB), also known as 7-hydroxycoumarin, is a derivative of coumarin, which is widely found in many plants such as carrots, coriander, and garden angelica. Although many studies have already revealed the various pharmacological properties of UMB, its effect on benign prostatic hyperplasia (BPH) remains unclear. Therefore, the present study aimed to elucidate the underlying mechanism of the anti-proliferative effect of UMB in a human benign prostatic hyperplasia cell line (BPH-1), as well as its ameliorative effect on BPH in testosterone propionate (TP)-induced rats. The results showed that UMB exerts an anti-proliferative effect in BPH-1 cells by modulating the signal transducer and activator of transcription 3 (STAT3)/E2F transcription factor 1 (E2F1) axis. UMB treatment not only inhibited androgen/androgen receptor (AR) signaling-related markers, but also downregulated the overexpression of G1/S phase cell cycle-related markers. In TP-induced rats, UMB administration demonstrated an anti-BPH effect by significantly reducing prostate size, weight, and epithelial thickness. In addition, UMB suppressed cell proliferation by reducing the expression of proliferating cell nuclear antigen (PCNA) and p-STAT3 (Tyr 705) in prostate tissue following TP injection. These findings suggest that UMB has pharmacological effects against BPH.

Oleanolic Acid Ameliorates Benign Prostatic Hyperplasia by Regulating PCNA-Dependent Cell Cycle Progression In Vivo and In Vitro.

Oleanolic acid (OA) is a natural, biologically active pentacyclic triterpenoid found in Cornus officinalis. Although C. officinalis and OA have antiproliferative actions, the effects and mechanisms of OA in benign prostatic hyperplasia (BPH) are unclear. We examined the effect of OA in an animal model of testosterone-induced BPH. Male rats were injected with testosterone propionate with or without OA. The inhibitory effect of OA on BPH-1 cells was determined in vitro. Rats with BPH exhibited outstanding BPH symptoms, including prostatic enlargement, upregulated dihydrotestosterone and 5α-reductase 2 levels, and histological changes. Compared with the BPH group, the OA group showed fewer pathological alterations and regular androgen events. OA inhibited prostate cell proliferation by downregulating the expression of proliferating cell nuclear antigen (PCNA) and cell cycle markers in BPH-induced animals. This indicated that OA has superior therapeutic effect in the BPH animal model than finasteride. In vitro studies demonstrated upregulation of PCNA and cell cycle proteins, whereas OA clearly reduced this upregulation. Thus, OA may inhibit the development of BPH by targeting cell cycle progression markers. These suggest that OA is a potential agent for BPH treatment.

Anti-Proliferative Effects of Standardized Cornus officinalis on Benign Prostatic Epithelial Cells via the PCNA/E2F1-Dependent Cell Cycle Pathway.

Cornus officinalis, widely used in traditional Chinese medicine, exhibits pharmacological effects against erectile dysfunction and pollakisuria, which are pathological symptoms of benign prostatic hyperplasia (BPH). Although traditional usage and a study on BPH have been reported, to our knowledge, no study has investigated the exact molecular mechanism(s) underlying the anti-proliferative effects of standardized C. officinalis on prostatic cells. We standardized C. officinalis 30% ethanol extract (COFE) and demonstrated the therapeutic effects of COFE on human BPH epithelial cells and testosterone-induced BPH in rats. In vitro studies using BPH-1 cells demonstrated an upregulation of BPH-related and E2F Transcription Factor 1(E2F1)-dependent cell cycle markers, whereas treatment with COFE clearly inhibited the proliferation of BPH epithelial cells and reduced the overexpression of G1 and S checkpoint genes. Additionally, COFE administration alleviated the androgen-dependent prostatic enlargement in a testosterone-induced BPH animal model. COFE exerted these anti-BPH effects by the inhibition of anti-apoptotic markers, suppression of PCNA expression, and regulation of E2F1/pRB-dependent cell cycle markers in rats with BPH. These results suggest that COFE exerts anti-proliferative effect by regulating PCNA/E2F1-dependent cell cycle signaling pathway both in vivo and in vitro. These findings reveal the therapeutic potential of COFE, which could be used as a substitute for BPH treatment.

HBX-6, Standardized Cornus officinalis and Psoralea corylifolia L. Extracts, Suppresses Benign Prostate Hyperplasia by Attenuating E2F1 Activation.

BACKGROUND: The aim of this study was to simplify and identify the contents of the herbal formula, HBX-5. This study was carried out to evaluate the therapeutic effects of HBX-6 in a mouse model of benign prostatic hyperplasia (BPH). Based on in vitro, we selected a candidate, reconstituted an experimental agent and investigated the effects on testosterone-induced BPH rats. Cell viability was determined by MTT assay in RWPE-1 and WPMY-1 cells. The expression of androgen receptor (AR) was measured in dihydrotestosterone-stimulated RWPE-1 and WPMY-1 cells. BPH was induced in mice by a subcutaneous injection of testosterone propionate for four weeks. Animals were divided into six groups: Group 1, control mice; Group 2, mice with BPH; Group 3, mice with BPH treated with finasteride; Group 4, mice with BPH treated with 200 mg/kg HBX-5; Group 5, mice with BPH treated with 100 mg/kg HBX-6; and Group 6, mice with BPH treated with 200 mg/kg HBX-6. Changes in prostate weight were measured after treatments, and the thickness of the epithelium was evaluated. The expression levels of proteins associated with prostatic cell proliferation and cell cycle-related proteins were determined. Based on previous reports and in vitro results, we selected Cornus officinalis and Psoralea corylifolia among HBX-5 components and reconstituted the experimental agent, and named it HBX-6. The result represented a new herbal formula, HBX-6 that suppressed the pathological alterations in BPH and showed a marked reduction in proliferation-related protein expression compared to mice with BPH. Our results indicate that HBX-6 has a better therapeutic effect in the BPH murine model than those of HBX-5 and finasteride, suggesting the role of HBX-6 as a new BPH remedial agent.

Anti-Proliferative Effects of HBX-5 on Progression of Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH), an age-dependent disorder with a prevalence percentage of 60% in the 60s, has been found to involve an androgenic hormone imbalance that causes confusion between cell apoptosis and proliferation. Because general medications for BPH treatment have undesirable side effects, the development of effective alternative medicines has been considered. HBX-5 is a newly developed formula with the aim of improving BPH, and is composed of nine medicinal herbs. BPH was induced in the rats by intramuscular injection of testosterone propionate after castration. Rats were divided into six groups, and the efficacy of HBX-5 on testosterone-induced BPH in rats was estimated. In addition, RWPE-1 and WPMY-1 cells were used to demonstrate the effect of HBX-5 on BPH in vitro model. Compared with the control group, HBX-5 administration group suppressed BPH manifestations, such as excessive development of prostate, and increase of serum dihydrotestosterone and 5α-reductase concentrations. Furthermore, immunohistochemistry analysis revealed that HBX-5 significantly decreased the expression of androgen receptor (AR) and proliferating cell nuclear antigen (PCNA). In addition, results of RWPE-1 and WPMY-1 cells showed that HBX-5 inhibited the over-expression of AR and PSA in DHT-induced prostate hyperplastic microenvironments.

Targeting benign prostate hyperplasia treatments: AR/TGF-ß/NOX4 inhibition by apocynin suppresses inflammation and proliferation.

INTRODUCTION: Apocynin (Apo), an NADPH oxidase (NOX) inhibitor, has been widely used to treat various inflammatory diseases. However, the therapeutic effects of Apo on benign prostatic hyperplasia (BPH), a multifactorial disease associated with chronic inflammation and hormone imbalance, remain unknown. OBJECTIVES: The link between androgen signaling, reactive oxygen species (ROS), and prostate cell proliferation may contribute to the pathogenesis of BPH; therefore, the aim of this study was to identify the specific signaling pathway involved and to demonstrate whether the anti-oxidant Apo plays a role in the prevention and treatment of BPH. METHODS: Ingenuity pathway analysis and si-RNA transfection were conducted to demonstrate the androgen receptor (AR) and NOX4 linkage in BPH. Pathological markers of BPH were measured by H&E staining, immunoblotting, ELISA, qRT-PCR, and immunofluorescence to examine the effect of Apo. Rats stimulated with testosterone and BPH-1 cells were used as BPH models. RESULTS: AR and NOX4 network-mediated oxidative stress was upregulated in the BPH model. Next, we examined the effects of Apo on oxidative stress and chronic prostatic inflammation in BPH mouse models. In a testosterone-induced BPH rat model, Apo alleviated pathological prostate enlargement and suppressed androgen/AR signaling. Apo suppressed the upregulation of proinflammatory markers and promoted the expression of anti-oxidant factors. Furthermore, Apo regulated the TGF-ß/Glut9/activin pathway and macrophage programming. In BPH-1 cells, Apo suppressed AR-mediated proliferation and upregulation of TGFB and NOX4 expression by alleviating oxidative stress. Apo activated anti-oxidant and anti-inflammatory systems and regulated macrophage polarization in BPH-1 cells. AR knockdown partially abolished the beneficial effects of Apo in prostate cells, indicating AR-dependent effects of Apo. CONCLUSION: In contrast with existing BPH therapies, Apo may provide a new application for prostatic disease treatment, especially for BPH, by targeting the AR/TGF-ß/NOX4 signaling pathway.

Anti-inflammatory Capacity of a Medicinal herb extract, Anemarrhena asphodeloides, on In vivo and In vitro models-induced atopic dermatitis.

Anemarrhena asphodeloides (AA) Bunge, a rhizomatous plant from the Liliaceae family, is traditionally utilized to manage inflammatory conditions. Nevertheless, its impact on atopic dermatitis (AD) and the associated molecular pathways have not yet been fully explored. This study explored the therapeutic effects of AA on AD both in vivo, using 2,4-dinitrofluorobenzene-induced NC/Nga mice, and in vitro, with tumor necrosis factor-α/interferon-γ-stimulated HaCaT keratinocytes. Topical application of AA ointment on the dorsal skin notably alleviated AD symptoms and skin lesions, enhanced the dermatitis score, and improved parameters such as the rate of trans-epidermal water loss, epidermal thickness, mast cell infiltration, systemic IgE levels, and cytokine expression. Furthermore, AA treatment significantly reduced serum levels of thymic stromal lymphopoietin (TSLP) and locally suppressed mRNA expression of thymus and activation-regulated chemokine (TARC) along with other relevant cytokines in affected skin. Both in vivo and in vitro applications of AA curtailed TSLP levels by inhibiting the expression of signal transducer and activator of transcription 6, a key regulator of pruritus and an initiator of mitogen-activated protein kinase signaling pathways. Additionally, AA affected the expression of tumor necrosis factor-like weak inducer of apoptosis/fibroblast growth factor-inducible 14, a pathway of interest in the study of cutaneous inflammatory diseases. Collectively, these findings propose that AA holds potential as an effective therapeutic agent for treating AD-induced skin inflammation.

Anti-Inflammatory Effect of Chestnut Honey and Cabbage Mixtures Alleviates Gastric Mucosal Damage.

Gastritis, one of the most common gastrointestinal disorders, damages the stomach lining as it causes a disproportion between the protective and ruinous factors of the gastric system. Cabbage (CB) is widely used to treat gastric lesions but requires the addition of natural sweeteners to counteract its distinct bitter taste. Therefore, this study sought to determine whether the combination of chestnut honey (CH)-which is known for its dark brown color and high kynurenic acid (KA) content-or KA-increased CH (KACH) with CB (CH + CB or KACH + CB) exerts synergistic effects for improving both taste and efficacy. Before confirming the gastroprotective effects in indomethacin (INDO)-induced rats, the anti-inflammatory activities of CH + CB and KACH + CB were assessed in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. As a result, treatment with either CH + CB or KACH + CB downregulated pro-inflammatory cytokine levels in LPS-stimulated RAW 264.7 macrophages by regulating the translocation of nuclear factor kappa B. Furthermore, both CH + CB and KACH + CB not only enhanced the levels of antioxidant enzymes but also triggered the activation of nuclear factor erythroid-related factor 2. Based on these effects, CH + CB or KACH + CB effectively protected the gastric mucosa in INDO-induced rats. Therefore, this study suggests that CH + CB and KACH + CB exert stronger gastroprotective effects when used together.

New Pimarane Diterpenoids Isolated from EtOAc-Extract of Apiospora arundinis Culture Medium Show Antibenign Prostatic Hyperplasia Potential.

Three new pimarane diterpenoids, libertellenones U-W (1-3), together with libertellenone C (4) and myrocin A (5) were isolated from an EtOAc-extract of Apiospora arundinis culture medium. The chemical structures of the new compounds were elucidated using MS, NMR, and CD spectroscopic data. Benign prostatic hyperplasia (BPH), the abnormal and pathological proliferation of epithelial and stromal cells in prostatic tissues, is a common disease in middle-aged and elderly men. In this study, the anti-BPH effects of myrocin A (5) were evaluated using BPH-1 and WPMY-1 cells. Treatment with myrocin A (5) exerted antiproliferative effects in BPH-1 and dihydrotestosterone (DHT)-stimulated WPMY-1 cells. In BPH, treatment with myrocin A (5) significantly suppressed the mRNA levels of androgen receptor (AR) and its downstream targets nuclear receptor coactivator 1 (NCOA1), proliferating cell nuclear antigen (PCNA) and kallikrein-related peptidase 3 (KLK3). Additionally, DHT-stimulated WPMY-1 cells demonstrated an upregulated mRNA levels of AR, NCOA1, PCNA, and KLK3. However, treatment with myrocin A (5) resulted in suppression of the mRNA levels. Moreover, myrocin A (5) docked computationally into the binding site of the androgen receptor (-5.5 kcal/mol).

Hesperidin ameliorates benign prostatic hyperplasia by attenuating cell proliferation, inflammatory response, and epithelial-mesenchymal transition via the TGF-ß1/Smad signaling pathway.

Excessively activated transforming growth factor-beta 1 (TGF-ß1) exacerbates benign prostatic hyperplasia (BPH) by triggering epithelial-mesenchymal transition (EMT) as well as epithelial and stromal cell differentiation. Hesperidin (HSP), a flavanone rich in citrus peels, exhibits a safe anti-cancer activity with few side effects. Although HSP reportedly inhibits cell growth in prostate cancer, studies on BPH have not yet been reported. Thus, this study aimed to figure out the therapeutic effect of HSP and its underlying mechanisms in BPH models in vivo and in vitro. To evaluate the anti-BPH effect of HSP in vivo, rats were injected with testosterone propionate (TP; 10 mg/kg, s.c.), finasteride (5 mg/kg, p.o.), and HSP (50 and 100 mg/kg, i.p.) for four weeks. The in vitro efficacy of HSP was evaluated using two prostate cell models, BPH-1 and dihydrotestosterone-stimulated WPMY-1 cells, for studying the interaction between epithelial and stromal cells. Both in vivo and in vitro, HSP inhibited prostate cell proliferation by suppressing the expression of androgen receptor-related markers. In addition, HSP reduced the expression levels of inflammatory and mesenchymal markers by blocking TGF-ß1 activation. Collectively, HSP alleviated BPH by attenuating prostate cell proliferation, the inflammatory response, and EMT by regulating the TGF-ß1/Smad signaling pathway. Thus, these results provide evidence for a new therapeutic approach against BPH.

Antioxidant mitoquinone suppresses benign prostatic hyperplasia by regulating the AR-NLRP3 pathway.

Mitoquinone (MitoQ), a mitochondria-targeted antioxidant, has been used to treat several diseases. The present study aimed to investigate the therapeutic effects of MitoQ in benign prostatic hyperplasia (BPH) models and their underlying molecular mechanisms. In this study, we determined that MitoQ inhibited dihydrotestosterone (DHT)-induced cell proliferation and mitochondrial ROS by inhibiting androgen receptor (AR) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling in prostate epithelial cells. Molecular modeling revealed that DHT may combine with AR and NLRP3, and that MitoQ inhibits both AR and NLRP3. AR and NLRP3 downregulation using siRNA showed the linkage among AR, NLRP3, and MitoQ. MitoQ administration alleviated pathological prostate enlargement and exerted anti-proliferative and antioxidant effects by suppressing the AR and NLRP3 signaling pathways in rats with BPH. Hence, our findings demonstrated that MitoQ is an inhibitor of NLPR3 and AR and a therapeutic agent for BPH treatment.

Morus alba fruits attenuates atopic dermatitis symptoms and pathology in vivo and in vitro via the regulation of barrier function, immune response and pruritus.

BACKGROUND: Morus alba fruits (MAF) belong to the Moraceae family, which are known to be effective in treating diabetic, autoimmune, and hormonal diseases owing to its low toxicity. MAF, as excerpted from Donguibogam, a representative Korean medical encyclopedia protected by UNESCO, has been widely used to treat lumbago, arthritis, and diabetes. Based on these effects, MAF is investigated for unidentified effects of atopic dermatitis, characterized by complex etiology of skin barrier dysfunction, inflammation, and chronic pruritus. METHODS: The antioxidant, inflammatory, and immunomodulatory properties of MAF and its bioactive compounds have been widely reported. According to an examination of 1-chloro-2,4-dinitrobenzene-induced AD-like skin lesions in NC/Nga mice, AD symptoms, such as increased dermatitis score, scratching frequency, immunoglobulin E, trans-epidermal water loss, epidermal thickness, and infiltration of mast cells, were relieved by topical MAF administration. They effectively attenuated cytokines and chemokines, such as interleukin (IL)-4, IL-5, IL-6, IL-8, IL-13, IL-17A, IL-22, IL-1ß, tumor necrosis factor-α, thymic stromal lymphopoietin (TSLP), thymic- and activation-regulated chemokine, normal T cell expression, and macrophage-derived chemokine secretion at the mRNA level in TNF-α/IFN-γ induced HaCaT (human immortalized keratinocyte) cells. RESULTS: Both in vivo and in vitro models, MAF increased the expression of filaggrin, involucrin, and loricrin, as well as inhibited the activation of Janus kinase 2, signal transducer and activator of transcription proteins 1, and mitogen-activated protein kinase pathways, including extracellular signal-regulated kinase, c-jun N-terminal kinase, and p38. Moreover, MAF reduced the expression of TSLP and periostin, which play important roles in skin pruritus as chronic pruritogenic factors. CONCLUSION: These data indicate that MAF could be used as a potential treatment for AD-like skin lesions by regulating the inflammatory response, improving physical skin barriers, and relieving symptomatic pruritus.

Anti-atopic dermatitis effect of fish collagen on house dust mite-induced mice and HaCaT keratinocytes.

Collagen, a major structural protein in mammalian tissues, is effective against skin wounds and osteoarthritis. Although bovine and porcine collagens have mainly been used, several potential risks of mammalian collagen have led to the use of fish collagen (FC) as an alternative. FC and its peptides are used as common cosmeceutical products because of their antihypertensive, anti-bacterial, and antioxidant activities. Despite the effects of FC on wrinkle reduction, UV-protection, and wound healing, the relationship between FC and atopic dermatitis (AD) has not yet been reported. Therefore, we investigated the anti-AD effects of FC against house dust mite (Dermatophagoides farinae, HDM)-induced AD in NC/Nga mice and TNF-α/IFN-γ-stimulated HaCaT keratinocytes. FC alleviated AD apparent symptoms, such as dermatitis score, transepidermal water loss, epidermal thickness, and mast cell infiltration upon declining pro-inflammatory cytokines and mediators, IL-6, IL-5, IL-13, TSLP, and TNF-α. The skin barrier protein, filaggrin, was also recovered by FC administration in vivo and in vitro. Immune response and skin barrier dysfunction are both mitigated by three routes of FC administration: oral, topical, and both routes via the regulation of IκB, MAPKs, and STATs pathways. In summary, FC could be a potential therapeutic agent for AD by regulating immune balance and skin barrier function.

Peucedanum japonicum Thunberg alleviates atopic dermatitis-like inflammation via STAT/MAPK signaling pathways in vivo and in vitro.

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disorder that exhibits clinical relapse. The disruption of the skin barrier increases the symptoms of AD, which is accompanied by a reduction in skin integrity. As an immune barrier, the skin plays a crucial role in regulating the inflammatory responses in AD. In this study, we used murine atopic dermatitis model using 2,4-dinitrochlorobenzen (DNCB), which is one of haptens to disrupt the skin barrier and generate the inflammation. As the small molecule, DNCB is easily penetrate the epidermis and binds to tissue proteins provoking immune responses. We evaluated the effects of an aqueous extract of Peucedanum japonicum Thunberg (PJT) in an experimental model of AD by measuring the mRNA and protein expression of cytokines and their related biomarkers. We examined the dorsal skin lesions, transepidermal water loss (TEWL), scratching behavior, expression of molecules related to skin barrier integrity, and histological changes in a murine model of DNCB- induced AD. We found out the down-regulatory effects of PJT on the AD-like symptoms or inflammatory dorsal lesions. For in vitro study, we used a mixture of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in human keratinocytes. The protein and mRNA expressions of skin barrier molecules and inflammatory markers were measured with western blotting and qRT-PCR assays, respectively. As a result, PJT alleviated the AD-like symptoms, and suppressed the inflammation caused by a TNF-α and IFN-γ in human keratinocytes. The regulatory effects of PJT appeared to be mediated via the mitogen-activated protein kinase (MAPK) and signal transducers and activators of transcription (STAT) signaling pathways both in vivo and in vitro. Altogether, the results indicated that PJT could serve as a promising therapeutic candidate for suppressing AD by inhibiting inflammation and improving the integrity of the skin barrier.

Euphorbia hirta Leaf Ethanol Extract Suppresses TNF-α/IFN-γ-Induced Inflammatory Response via Down-Regulating JNK or STAT1/3 Pathways in Human Keratinocytes.

Skin inflammation may cause allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis. Euphorbia hirta (E. hirta) is a member of the Euphorbiaceae family and is well-known for its anti-asthma effects. E. hirta has traditionally been used to treat respiratory ailments, dysentery, jaundice, and digestive problems. However, its effects on skin inflammation remain unclear. Here, we determined the effects of 70% ethanol extract of E. hirta leaves (ELE) in vitro using human keratinocyte HaCaT cells, which constitute most epidermal skin cells. We determined the inhibitory effects of ELE on the inflammation caused by tumor necrosis factor (TNF)-α/interferon (IFN)-γ in keratinocytes using ELISA, immunoblotting, and qRT-PCR assay. ELE was found to reduce the production and mRNA expression of pro-inflammatory cytokines such as TNF-α or interleukin-6 and the expression of various proteins, including signal transducers, activators of transcription 1/3, and mitogen-activated protein kinase. Expression levels of these proteins were found to be upregulated in the TNF-α/IFN-γ-stimulated condition and downregulated by ELE treatment. These results indicate that ELE protects HaCaT cells against TNF-α/IFN-γ-induced skin inflammation.

Purple Corn Extract Improves Benign Prostatic Hyperplasia by Regulating Prostate Cell Proliferation and Apoptosis.

Purple corn (Zea mays L.), utilized as a natural pigment in food production and processing, has been used to treat obesity, cystitis, and urinary tract infections. However, no reports of its use for benign prostatic hyperplasia (BPH) exist. Purple corn extract (PCE) contains anthocyanins, particularly cyanidin-3-O-glucoside, which have various pharmacological characteristics. Therefore, this study sought to elucidate the ameliorative effect of PCE on BPH in dihydrotestosterone (DHT)-stimulated WPMY-1 cells and testosterone propionate (TP)-induced rats. Expression levels of the upregulated androgen receptor (AR) and its related genes in DHT-stimulated WPMY-1 cells were reduced by PCE, and proapoptotic gene expression increased by modulating the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling cascade. PCE reduced the weight of the enlarged prostate by inhibiting the androgen/AR signaling-related markers. Histological variations in the prostate epithelium caused by TP injection were restored by PCE. Thus, PCE alleviates BPH by modulating prostate cell proliferation and apoptosis.