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Herbal combinations of Rhei Radix et Rhizoma, Gardeniae Fructus, Cimicifugae Rhizoma, and Ginseng Radix have been used in traditional formulas to treat the symptoms of heat and dryness. This study investigated the therapeutic effects of a natural compound mixture (PSM) of these herbal combinations, containing emodin, genipin, chlorogenic acid, cimigenoside, and ginsenoside Rb1, for the treatment of psoriasis and its underlying molecular mechanisms. PSM was applied topically to the dorsal skin lesions of imiquimod- (IMQ-) induced C57BL/6 mice, and the expression of the proinflammatory mediators was investigated. The topical application of 1% PSM reduced psoriasis-like symptoms in IMQ-induced C57BL/6 mice significantly. PSM also attenuated the production of IFN-γ, IL-1β, and IL-6 in skin lesions. Histological analysis showed that PSM had antipsoriatic effects by reducing the lesional epidermal thickness. Either M5 (IL-1α, IL-17A, IL-22, oncostatin M, and TNF-α, 10 ng/ml each) or IL-22- (100 ng/ml) stimulated HaCaT cells were used to examine the efficacy and underlying mechanism of PSM. In M5-stimulated HaCaT cells, PSM inhibited the production of C-X-C motif chemokine ligand (CXCL) 10 and C-C motif chemokine ligand (CCL) 20 effectively. Moreover, compared to the use of a single compound, it had synergistic inhibitory effects in CXCL8 production. PSM suppressed the phosphorylation of ERK1/2, p38, and STAT3 signaling pathways in M5-stimulated HaCaT cells. Furthermore, PSM reduced the proliferation rate and K16 and K17 expressions in IL-22-stimulated HaCaT cells by inhibiting the Akt/mTOR signaling pathway. These results suggest that PSM may have a therapeutic potential in the treatment of psoriasis lesions.

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Non-small-cell lung cancer (NSCLC) is the most frequent cause of cancer-related death. In this study, we found the anticancer activity of lotus seedpod extract (LSPE) in NSCLC cells, since LSPE treatment inhibited cell proliferation of A549 and H460 cells in a dose-dependent manner and the clonogenic activities of LSPE-treated cells were also reduced. In LSPE-treated cells, the cleavage of poly (ADP-ribose) polymerase (PARP) and phosphorylation of H2X, were also observed, indicating the pro-apoptotic effect of LSPE. Next, we found that LPSE treatment diminished the levels of protein and mRNA of Axl, a receptor tyrosine kinase (RTK) that transduces critical signals for cell proliferation and inhibition of apoptosis. The promoter activity of Axl was found to be dose-dependently decreased in response to LSPE treatment, implying that LSPE inhibited Axl gene expression at transcriptional level. In addition, Axl overexpression was found to decrease the effects of LSPE on inhibition of cell proliferation and colony formation as well as induction of PARP cleavage and phosphorylation of H2AX, while the same activities of LPSE were increased by knockdown of Axl gene expression, indicating that the antiproliferative and pro-apoptotic effect of LSPE is inversely proportional to the protein level of Axl. Taken together, we found that the LSPE suppressed cell proliferation and induced apoptosis of NSCLC cells, which is attenuated or augmented by overexpression or RNA interference of Axl expression, respectively. Our data suggest that Axl is a novel therapeutic target of LSPE to inhibit cell proliferation and promote apoptosis in NSCLC cells. Practical applications In this study, lotus seedpod extract (LSPE) was found to have the cytotoxic and apoptosis-inducing potentials in non-small-cell lung cancer (NSCLC) cells. LSPE downregulated the Axl expression at transcriptional level and the effects of LSPE on cell proliferation as well as apoptosis were affected by Axl protein level. Therefore, the inference of Axl-mediated intracellular signals by LSPE must be a novel approach to control NSCLC.

The delayed and impaired wound healing caused by dexamethasone (DEX) is commonly reported. Puerarin, the major isoflavone found in Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep promoted the wound healing process in diabetic rats. However, the effects and underlying mechanisms of puerarin on DEX-impaired wound healing have not been investigated. This study examined the potential uses of puerarin in upregulating keratinocyte proliferation and migration in dexamethasone (DEX)-suppressed wound healing model. The effects of puerarin on wound healing in vivo were investigated by taking full-thickness 5 mm punch biopsies from the dorsal skin of BALB/c mice and then treating them topically with 0.1% DEX. For the in vitro study, DEX-treated HaCaT cells were used to examine the effects of puerarin on DEX-induced keratinocyte proliferation and migration and the mechanisms of its action. Puerarin, when applied topically, accelerated the wound closure rate, increased the density of the capillaries, and upregulated the level of collagen fibers and TGF-β in the wound sites compared to the DEX-treated mice. Puerarin promoted the proliferation and migration of keratinocytes by activating the ERK and Akt signaling pathways in DEX-treated HaCaT cells. In conclusion, puerarin could be effective in reversing delayed and disrupted wound healing associated with DEX treatments.

Background: Oenothera biennis (evening primrose) produces bioactive substances with a diverse range of pharmacological functions. However, it is currently unknown whether extract prepared from the aerial parts of O. biennis (APOB) can protect the skin against oxidative stress. Objective: The aim of this study is to investigate the protective effects of APOB against oxidative stress-induced damage in human skin keratinocytes (HaCaT) and elucidate the underlying mechanisms. Methods: We pretreated HaCaT cells with various concentrations of APOB or the antioxidant N-acetyl-L-cysteine before applying H2O2. We then compared the cell viability, intracellular reactive oxygen species (ROS) production, and DNA and mitochondrial damage between pretreated and untreated control cells using a range of assays, flow cytometry, and Western blot analysis and also examined the reducing power and DPPH free radical scavenging activity of APOB. Results: APOB pretreatment significantly increased cell viability, effectively attenuated H2O2-induced comet tail formation, and inhibited H2O2-induced phosphorylation of the histone γH2AX, as well as the number of apoptotic bodies and Annexin V-positive cells. APOB was found to have high reducing power and DPPH radical scavenging activity and also exhibited scavenging activity against intracellular ROS accumulation and restored the loss of mitochondrial membrane potential caused by H2O2. APOB pretreatment almost totally reversed the enhanced cleavage of caspase-3, the degradation of poly (ADP-ribose)-polymerase (PARP), DNA fragmentation that usually occurs in the presence of H2O2, and increased the levels of heme oxygenase-1 (HO-1), a potent antioxidant enzyme that is associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). Conclusions: APOB can protect HaCaT cells from H2O2-induced DNA damage and cell death by blocking cellular damage related to oxidative stress via a mechanism that affects ROS elimination and by activating the Nrf2/HO-1 signaling pathway.

Forsythiae Fructus, Lonicerae Flos, and Scutellariae Radix are medicinal herbs that possess anti-inflammatory and anti-atopic effects. Hence, we investigated the effects of a mixture (ADM), containing arctigenin, hederagenin, and baicalein, which are the main compound from these herbs on atopic dermatitis (AD) skin lesions and the underlying molecular mechanisms. ADM was topically applied to dorsal skin lesions of 2,4-dinitrochlorobenzene- (DNCB-) induced ICR mice, and the expressions of proinflammatory mediators and HPA axis hormones were investigated. The topical application of 0.5% ADM significantly reduced the DNCB-induced symptoms of AD in ICR mice. Histological analysis showed that ADM exerted antiatopic effects by reducing the epidermal thickness and mast cell infiltration into skin lesions. 0.5% ADM attenuated the levels of TNF-α, IFN-γ, IL-4, and VEGF in skin lesions and serum IgE. The production of Th1-/Th2-related cytokines in splenic tissues, including TNF-α, IFN-γ, IL-12, and IL-4, were also decreased by ADM treatment. ADM diminished corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosteroid (CORT) production in DNCB-induced mice. In vitro, ADM reduced the productions of TARC/CCL17, MDC/CCL22, IL-6, and ICAM-1 in TNF-α/IFN-γ- (TI-) stimulated HaCaT cells by suppressing the ERK and JNK signaling pathways. In addition, ADM inhibited corticotropin-releasing hormone/substance P- (CRH/SP-) induced VEGF production in HMC-1 cells. These results suggest that ADM may have therapeutic potential in AD by reducing inflammation and attenuating HPA axis activation.