Compared Burden of Psoriasis, Atopic Dermatitis, Hidradenitis Suppurativa, and Chronic Urticaria: Baseline Characteristics of the Patients Included in the OMCCI Cohort - A French, Prospective Multicenter Study of Chronic Inflammatory Dermatoses.

INTRODUCTION: Chronic inflammatory dermatoses (CIDs) can significantly affect patients' lives. The Observatory of Chronic Inflammatory Skin Diseases (OMCCI) cohort was initiated to quantify the impact and disease evolution of four CID over 4 years' follow-up; at least 1,000 patients per CID are planned to be enrolled. The objective of this study was to present baseline characteristics of patients included in the OMCCI cohort between December 2020 and September 2022. METHODS: This French, prospective, multicenter registry included adult patients treated in daily practice for moderate-to-severe psoriasis (PS), atopic dermatitis (AD), hidradenitis suppurativa (HS), or chronic urticaria (CU) starting or modifying a systemic treatment. At the inclusion visit and then every 6 months during 4 years, patient-reported outcomes and data on these diseases and their treatments are recorded. RESULTS: A total of 2,058 patients from 24 centers were included: 1,137 PS, 413 AD, 301 HS, and 207 CU. Of these, 1,950 patients started or changed systemic treatment, and 108 reduced the dose of existing systemic treatment. Disease impact was qualified as debilitating by 80.1% (PS), 90.5% (AD), 90.5% (HS), and 89.4% (CU), affecting daily, family, and professional life. According to the SF-12 Survey, the impact of all four diseases was borderline pathological for physical health and severe for mental health. At inclusion, 20.4% of patients were receiving a conventional systemic or biologic treatment. After the first visit, this percentage raised to 83.3%. During the 6 months preceding study inclusion, 17.7% (PS), 27.9% (AD), 43.1% (HS), and 43.6% (CU) of patients missed work due to their illness, and 26.3% of patients with HS had been admitted to hospital (vs. 8.1%, 5.8%, and 13% of patients with PS, AD, or CU, respectively). CONCLUSION: These CIDs (especially HS) had a major impact on all aspects of patients' quality of life. The low baseline use of systemic drugs and the high burden of these CIDs suggest that these agents are underused. Long-term and dynamic evaluation of the changes brought by the initiation or optimization of these treatments on the evolution of patients' lives will be studied prospectively during the 4-year follow-up of the OMCCI.

Evolution of dupilumab-associated conjunctivitis in patients with atopic dermatitis after switching dupilumab to tralokinumab or Janus kinase inhibitors (RESO-ADOC study).

BACKGROUND: Clinical trials and real-life data have reported an increased incidence of conjunctivitis in patients treated with dupilumab for their atopic dermatitis (AD). Although mostly mild in severity, in some cases conjunctivitis will appear or increase after dupilumab initiation, which can lead to dupilumab discontinuation. OBJECTIVES: (1) To describe the characteristics of patients developing conjunctivitis requiring discontinuation of dupilumab; and (2) to analyse the factors associated with a complete conjunctivitis improvement after dupilumab discontinuation and a switch to tralokinumab or Janus kinase inhibitors. METHODS: This was a multicentre retrospective cohort study that included all patients with AD treated with dupilumab who developed conjunctivitis leading to dupilumab discontinuation and switching to tralokinumab or Janus kinase inhibitors in daily practice. Data on patients, their AD and conjunctivitis were analysed at the inclusion visit (corresponding to discontinuation of dupilumab and the institution of new AD treatment), at visit 2 (3-6 months after inclusion) and at visit 3 (corresponding to the last medical visit). RESULTS: After multivariate analysis, the only factors associated with a complete resolution of dupilumab-associated conjunctivitis at visit 2 and/or visit 3 were conjunctivitis duration (OR 8.98, 95% CI 1.47-55) (p = 0.018), personal history of asthma (OR 10.66, 95% CI 1.82-62.63) (p = 0.009) and switching from dupilumab to Janus kinase inhibitors (OR 17.11, 95% CI 2.94-99.66) (p = 0.002). CONCLUSIONS: Although uncommon, severe dupilumab-associated conjunctivitis is more frequent in daily life compared to its incidence in the dupilumab pivotal trials. In these cases, our study suggests that a rapid switch to another molecule, particularly a Janus kinase inhibitor, should be considered.

Anti-BP180 IgG antibody ELISA values correlate with adverse pregnancy outcomes in pemphigoid gestationis.

BACKGROUND: Adverse pregnancy outcomes (APO) occur in 35% of patients with pemphigoid gestationis (PG). No biological predictor of APO has been established yet. OBJECTIVES: To assess a potential relationship between the occurrence of APO and the serum value of anti-BP180 antibodies at the time of PG diagnosis. METHODS: Multicentre retrospective study conducted from January 2009 to December 2019 in 35 secondary and tertiary care centres. INCLUSION CRITERIA: (i) diagnosis of PG according to clinical, histological and immunological criteria, (ii) ELISA measurement of anti-BP180 IgG antibodies determined at the time of PG diagnosis with the same commercial kit and (iii) obstetrical data available. RESULTS: Of the 95 patients with PG included, 42 had one or more APO, which mainly corresponded to preterm birth (n = 26), intrauterine growth restriction (IUGR) (n = 18) and small weight for gestational age at birth (n = 16). From a ROC curve, we identified a threshold of 150 IU ELISA value as the most discriminating to differentiate between patients with or without IUGR, with 78% sensitivity, 55% specificity, 30% positive and 91% negative predictive value. The threshold >150 IU was confirmed using a cross-validation based on bootstrap resampling, which showed that the median threshold was 159 IU. Upon adjusting for oral corticosteroid intake and main clinical predictors of APO, an ELISA value of >150 IU was associated with the occurrence of IUGR (OR = 5.11; 95% CI: 1.48-22.30; p = 0.016) but not with any other APO. The combination of blisters and ELISA values higher than 150 IU led to a 2.4-fold higher risk of all-cause APO (OR: 10.90; 95% CI: 2.33-82.3) relative to patients with blisters but lower values of anti-BP180 antibodies (OR of 4.54; 95% CI 0.92-34.2). CONCLUSION: These findings suggest that anti-BP180 antibody ELISA value in combination with clinical markers is helpful in managing the risk of APO, in particular IUGR, in patients with PG.

Narrow resection margins are not associated with mortality or recurrence in patients with Merkel cell carcinoma: A retrospective study.

BACKGROUND: Wide local excision constitutes the standard of care for Merkel cell carcinoma, but the optimal margin width remains controversial. OBJECTIVES: To assess whether narrow margins (0.5-1 cm) were associated with outcome. METHODS: Patients were recruited from a retrospective French multicentric cohort and included if they had had excision of primary tumor with minimum lateral margins of 0.5 cm. Factors associated with mortality and recurrence were assessed by multivariate regression. RESULTS: Among the 214 patients included, 58 (27.1%) had undergone excision with narrow margins (0.5-1 cm) versus 156 (72.9%) with wide margins (>1 cm). During a median follow-up of 50.7 months, cancer-specific survival did not differ between groups (5-year specific survival rate 76.8% [95% confidence interval 61.7%-91.9%] and 76.2% [95% confidence interval 68.8%-83.6%], respectively). Overall survival, any recurrence-free survival, and local recurrence-free survival did not significantly differ between groups. Cancer-specific mortality was associated with age, male sex, American Joint Committee on Cancer stage III, and presence of positive margins. LIMITATIONS: Retrospective design, heterogenous baseline characteristics between groups. CONCLUSION: Excision with narrow margins was not associated with outcome in this cohort, in which most patients had clear margins and postoperative radiation therapy. Residual tumor, mostly found on deep surgical margins, was independently associated with prognosis.

Socioeconomic Inequalities and Severity of Plaque Psoriasis at a First Consultation in Dermatology Centers.

Psoriasis has major physical, psychological, and social impacts: its management should not be restricted by individual financial considerations in Western countries as these have well-structured health systems and social/insurance coverage. We investigated if the socioeconomic characteristics of patients were associated with severity of psoriasis and access to healthcare. In a cross-sectional study, we included 903 patients with psoriasis that were consulting for the first time. We showed that low educational level was associated with severity of disease in multivariate analyses. Moreover, patients of lower class and lower educational level, with severe psoriasis, had seen fewer physicians and had less frequently received a systemic treatment. Thus, physicians need to be vigilante of patients with a low socioeconomic status. Both low socioeconomic status and less access to dermatologists are associated with clinical severity of psoriasis at a first consultation.

Frequency and Risk Factors for Associated Lymphomas in Patients With Lymphomatoid Papulosis.

BACKGROUND: Lymphomatoid papulosis (LyP) is classified as an indolent cutaneous lymphoma, but outcome dramatically worsens if LyP is associated with lymphoma. The frequency of this association remains unclear in the literature. Here, we assess the frequency and risk factors of association between LyP and another lymphoma in an 11-year retrospective study conducted in 8 dermatology departments belonging to the French Study Group on Cutaneous Lymphoma (FSGCL). PATIENTS AND METHODS: Patients with LyP were identified and data extracted from the FSGCL registry between 1991 and 2006. Patients were followed up to January 2014. Age, sex, number of skin lesions, histologic subtype, and genotype were recorded at baseline. Risk factors were determined using univariate and multivariate analysis. Cumulative probability of association was calculated using the Kaplan-Meier method. RESULTS: We observed 52 cases of lymphomas (cutaneous, n = 38; systemic, n = 14) in 44 of 106 patients (41%). Lymphoma diagnosis was concomitant with or prior to LyP diagnosis in 31 cases and occurred during the course of LyP in 21 cases (cutaneous, n = 14; systemic, n = 7; median delay: 5 years; interquartile range: 1.5-7 years). In multivariate analysis, main prognostic factors for association between LyP and another lymphoma were older age (odds ratio [OR]: 1.05 per year; 95% confidence interval [CI]: 1.01-1.08; p = .011) and presence of a T-cell clone in LyP lesions (OR: 7.55; 95% CI: 2.18-26.18; p = .001). CONCLUSION: Older age and presence of a T-cell clone in LyP lesions are risk factors for associated lymphomas in patients with LyP. These findings should help to identify patients who require close management in clinical practice. IMPLICATIONS FOR PRACTICE: The management of lymphomatoid papulosis (LyP) is that of an indolent cutaneous lymphoma, based on its excellent prognosis. However, this good prognosis is altered if LyP is associated with lymphoma. Furthermore, risk factors for and frequency of this association remain unclear in the literature. The results presented here demonstrate a high rate of association between LyP and other lymphomas (41%) as well as a long median delay of occurrence (5 years), which emphasizes the need for prolonged follow-up of patients with LyP. Moreover, two main risk factors (i.e., older age and presence of a T-cell clone in LyP lesions) are highlighted, which should help clinical practitioners to identify patients who require close management.

A high neutrophil-to-lymphocyte ratio as a potential marker of mortality in patients with Merkel cell carcinoma: A retrospective study.

BACKGROUND: The prognostic relevance of a high blood neutrophil-to-lymphocyte ratio (NLR) has been reported in many cancers, although, to our knowledge, not investigated in patients with Merkel cell carcinoma (MCC) to date. OBJECTIVE: We assessed whether the NLR at baseline was associated with specific survival and recurrence-free survival in MCC. METHODS: We retrospectively included MCC cases between 1999 and 2015 and collected clinical data, blood cell count at baseline, and outcome. A Cox model was used to identify factors associated with recurrence and death from MCC. RESULTS: Among the 75 patients included in the study, a high NLR at baseline (NLR ≥4) was associated with death from MCC in univariate (hazard ratio 2.76, 95% confidence interval 1.15-6.62, P = .023) and multivariate (hazard ratio 3.30, 95% confidence interval 1.21-9.01, P = .020) analysis, but not with recurrence. LIMITATIONS: Because of the retrospective design, we excluded patients with missing data and not all confounding factors that may influence the NLR were available. CONCLUSION: A high NLR at baseline was independently associated with specific mortality in patients with MCC. The NLR seems to constitute an easily available and inexpensive prognostic biomarker at baseline.

Somatostatin Receptors 2A and 5 Are Expressed in Merkel Cell Carcinoma with No Association with Disease Severity.

BACKGROUND/AIMS: Merkel cell carcinoma (MCC) is a rare high-grade neuroendocrine tumour of the skin. It has been speculated that MCCs express somatostatin receptors (SSTRs), but this has never been assessed in a large series of MCCs. The main aim of this study was to assess the expression of SSTR2A and SSTR5 in MCC tumours. The secondary aims were to assess whether expression of SSTR was associated with the Ki67 proliferative index, Merkel cell polyomavirus (MCPyV) status, clinical characteristics and outcome. METHODS: Clinical data and tumours were collected from an ongoing cohort of French patients with MCC. Immunohistochemistry was performed with anti-SSTR2A and anti-SSTR5 monoclonal antibodies, and tumours were classified into 3 groups: 'no expression', 'low expression' and 'moderate expression' using an SSTR staining score. RESULTS: SSTR expression was assessed for 105 MCC tissue samples from 98 patients, and clinical characteristics were available for 87 of them. SSTR expression was consistent between the primary skin tumour and the corresponding metastases for SSTR2A and SSTR5 in 3/7 and 6/7 cases, respectively. SSTR2A and SSTR5 were expressed in 58 cases (59.2%) and in 44 cases (44.9%), respectively. Overall, at least one SSTR was expressed in 75 tumours (76.5%). SSTR expression was not associated with clinical characteristics, Ki67 proliferative index, recurrence-free survival or MCC-specific survival. Expression of SSTR2A was associated with MCPyV status in MCC tumours but not SSTR5. CONCLUSION: SSTRs were expressed in a high proportion of MCCs, although expression was heterogeneous between tumours and was not associated with disease severity.

[Cutaneous lymphoid hyperplasia (pseudolymphoma) on the red dye of a tattoo]. / Hyperplasie lymphoïde chronique (pseudolymphome) sur l'encre rouge de tatouage.

Cutaneous lymphoid hyperplasia (pseudolymphoma) on tattoo is rare. The diagnosis is histological. We report a case of cutaneous lymphoid hyperplasia within the red ink of a tattoo found on a 35-year-old man presenting multiple infiltrated nodules confined to the red areas of his tattoo, which he had done 2 months ago. The pathological examination showed a diffuse lympho-histiocytic dermo-hypodermal infiltrate, associated with a lichenoid reaction. Immunohistochemistry displayed T-cell infiltration (CD3+, CD5+, CD8+). The treatment is difficult, knowing that the spontaneous regression seems possible, and the progression into a lymphoma is exceptional in the case of a chronic evolution over a number of years.

Smooth Muscle Cells of Dystrophic (mdx) Mice Are More Susceptible to Hypoxia; The Protective Effect of Reducing Ca2+ Influx.

Duchenne muscular dystrophy (DMD) is an inherited muscular disorder caused by mutations in the dystrophin gene. DMD patients have hypoxemic events due to sleep-disordered breathing. We reported an anomalous regulation of resting intracellular Ca2+ ([Ca2+]i) in vascular smooth muscle cells (VSMCs) from a mouse (mdx) model of DMD. We investigated the effect of hypoxia on [Ca2+]i in isolated and quiescent VSMCs from C57BL/10SnJ (WT) and C57BL/10ScSn-Dmd (mdx) male mice. [Ca2+]i was measured using Ca2+-selective microelectrodes under normoxic conditions (95% air, 5% CO2) and after hypoxia (glucose-free solution aerated with 95% N2-5% CO2 for 30 min). [Ca2+]i in mdx VSMCs was significantly elevated compared to WT under normoxia. Hypoxia-induced [Ca2+]i overload, which was significantly greater in mdx than in WT VSMCs. A low Ca2+ solution caused a reduction in [Ca2+]i and prevented [Ca2+]i overload secondary to hypoxia. Nifedipine (10 µM), a Ca2+ channel blocker, did not modify resting [Ca2+]i in VSMCs but partially prevented the hypoxia-induced elevation of [Ca2+]i in both genotypes. SAR7334 (1 µM), an antagonist of TRPC3 and TRPC6, reduced the basal and [Ca2+]i overload caused by hypoxia. Cell viability, assessed by tetrazolium salt (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced in mdx compared to WT VSMCs. Pretreatment with SAR7341 increases cell viability in normoxic mdx (p < 0.001) and during hypoxia in WT and mdx VSMCs. These results provide evidence that the lack of dystrophin makes VSMCs more susceptible to hypoxia-induced [Ca2+]i overload, which appears to be mediated by increased Ca2+ entry through L-type Ca2+ and TRPC channels.

Implication of the ryanodine receptor in TRPV4-induced calcium response in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats.

There is a growing body of evidence indicating that transient receptor potential (TRP) channels are implicated in calcium signaling and various cellular functions in the pulmonary vasculature. The aim of this study was to investigate the expression, functional role, and coupling to reticulum calcium channels of the type 4 vanilloid TRP subfamily (TRPV4) in the pulmonary artery from both normoxic (Nx) and chronically hypoxic (CH) rats. Activation of TRPV4 with the specific agonist 4α-phorbol-12,13-didecanoate (4α-PDD, 5 µM) increased the intracellular calcium concentration ([Ca(2+)](i)). This effect was significantly reduced by a high concentration of ryanodine (100 µM) or chronic caffeine (5 mM) that blocked ryanodine receptor (RyR) but was insensitive to xestospongin C (10 µM), an inositol trisphosphate receptor antagonist. Inhibition of RyR1 and RyR3 only with 10 µM of dantrolene did not attenuate the 4α-PDD-induced [Ca(2+)](i) increase. Western blotting experiments revealed the expression of TRPV4 and RyR2 with an increase in both receptors in pulmonary arteries from CH rats vs. Nx rats. Accordingly, the 4α-PDD-activated current, measured with patch-clamp technique, was increased in pulmonary artery smooth muscle cells (PASMC) from CH rats vs. Nx rats. 4α-PDD increased isometric tension in artery rings, and this response was also potentiated under chronic hypoxia conditions. 4α-PDD-induced calcium response, current, and contraction were all inhibited by the selective TRPV4 blocker HC-067047. Collectively, our findings provide evidence of the interplay between TRPV4 and RyR2 in the Ca(2+) release mechanism and contraction in PASMC. This study provides new insights onto the complex calcium signaling in PASMC and point out the importance of the TRPV4-RyR2 signaling pathway under hypoxic conditions that may lead to pulmonary hypertension.

Cardioprotective Effect of Whole Body Periodic Acceleration in Dystrophic Phenotype mdx Rodent.

Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting and the development of a dilated cardiomyopathy (DCM), which is the leading cause of death in DMD patients. Despite knowing the cause of DMD, there are currently no therapies which can prevent or reverse its inevitable progression. We have used whole body periodic acceleration (WBPA) as a novel tool to enhance intracellular constitutive nitric oxide (NO) production. WBPA adds small pulses to the circulation to increase pulsatile shear stress, thereby upregulating endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) and subsequently elevating the production of NO. Myocardial cells from dystrophin-deficient 15-month old mdx mice have contractile deficiency, which is associated with elevated concentrations of diastolic Ca2+ ([Ca2+]d), Na+ ([Na+]d), and reactive oxygen species (ROS), increased cell injury, and decreased cell viability. Treating 12-month old mdx mice with WBPA for 3 months reduced cardiomyocyte [Ca2+]d and [Na+]d overload, decreased ROS production, and upregulated expression of the protein utrophin resulting in increased cell viability, reduced cardiomyocyte damage, and improved contractile function compared to untreated mdx mice.

Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis.

Osteoarthritis (OA) is a complex degenerative disease in which joint homeostasis is disrupted, leading to synovial inflammation, cartilage degradation, subchondral bone remodeling, and resulting in pain and joint disability. Yet, the development of new treatment strategies to restore the equilibrium of the osteoarthritic joint remains a challenge. Numerous studies have revealed that dietary components and/or natural products have anti-inflammatory, antioxidant, anti-bone-resorption, and anabolic potential and have received much attention toward the development of new therapeutic strategies for OA treatment. In the present review, we provide an overview of current and emerging natural-product-based research treatments for OA management by drawing attention to experimental, pre-clinical, and clinical models. Herein, we review current and emerging natural-product-based research treatments for OA management.

Psychometric validation of a patient-reported outcome questionnaire (Qualipsosex) assessing the impact of psoriasis and psoriatic arthritis on patient perception of sexuality.

ABSTRACT: Psoriasis (Pso) and psoriatic arthritis (PsA) frequently have a negative impact on patients' sexual health. We have developed a specific questionnaire assessing the impact of Pso and PsA on patient perception of sexuality: the QualipsoSex Questionnaire (QSQ). The aim of the present study was to further validate this questionnaire by checking its psychometric properties including validity, reliability, and responsiveness.A cross sectional observational study with a longitudinal component for responsiveness and test-retest reliability was performed in 12 centers in France including 7 dermatologists and 5 rheumatologists. Psychometric properties were examined according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) check-list.At baseline, 114 patients had Pso and 35 patients had PsA including 17 peripheral arthritis, 4 axial disease, 13 patients with both axial disease and peripheral arthritis and one patient with an undifferentiated phenotype. The mean Pso Area and Severity Index score was 12.5. Genital organs were involved in 44.7% of Pso cases. Internal consistency, construct validity, and reliability were good with Cronbach's α coefficient, measure of sampling adequacy and intraclass correlation coefficient respectively at 0.87, 0.84, and 0.93. The QSQ also demonstrated acceptable sensitivity to change.The QSQ has demonstrated good psychometric properties fulfilling the validation process relative to the recommendations of the COSMIN check list. The QSQ is simple to score and may hopefully be valuable in clinical practice and in clinical trials.

Contribution of TRPC Channels to Intracellular Ca2 + Dyshomeostasis in Smooth Muscle From mdx Mice.

Duchenne muscular dystrophy (DMD) is an irreversible muscle disease characterized by a progressive loss of muscle function, decreased ambulation, and ultimately death as a result of cardiac or respiratory failure. DMD is caused by the lack of dystrophin, a protein that is important for membrane stability and signaling in excitable cells. Although vascular smooth muscle cells (VSMCs) dysfunction occurs in many pathological conditions, little is known about vascular smooth muscle function in DMD. We have previously shown that striated muscle cells, as well as neurons isolated from dystrophic (mdx) mice have higher intracellular Ca2+ ([Ca2+]i) and Na+ ([Na+]i) concentrations and decreased cell viability in comparison with wild type (Wt). Experiments were carried out in isolated VSMCs from mdx (a murine model of DMD) and congenic C57BL/10SnJ Wt mice. We found elevated [Ca2+]i and [Na+]i in VSMCs from mdx mice compared to Wt. Exposure to 1-oleoyl-2-acetyl-sn-glycerol (OAG), a TRPC3 and TRPC6 channel activator, induced a greater elevation of [Ca2+]i and [Na+]i in mdx than Wt VSMCs. The OAG induced increases in [Ca2+]i could be abolished by either removal of extracellular Ca2+ or by SAR7334, a blocker of TRPC3 and TRPC 6 channels in both genotypes. Mdx and Wt VSMCs were susceptible to muscle cell stretch-induced elevations of [Ca2+]i and [Na+]i which was completely inhibited by GsMTx-4, a mechanosensitive ion channel inhibitor. Western blots showed a significant upregulation of TRPC1 -3, -6 proteins in mdx VSMCs compare to age-matched Wt. The lack of dystrophin in mdx VSMCs produced a profound alteration of [Ca2+]i and [Na+]i homeostasis that appears to be mediated by TRPC channels. Moreover, we have been able to demonstrate pharmacologically that the enhanced stretch-induced elevation of intracellular [Ca2+] and concomitant cell damage in mdx VSMCs also appears to be mediated through TRPC1, -3 and -6 channel activation.

Andrographis paniculata and Its Bioactive Diterpenoids Against Inflammation and Oxidative Stress in Keratinocytes.

Andrographis paniculata was widely used in traditional herbal medicine to treat various diseases. This study explored the potential anti-aging activity of Andrographis paniculata in cutaneous cells. Human, adult, low calcium, high temperature (HaCaT) cells were treated with methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12). Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by fluorescence using a 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe and cytokines were quantified by ELISA for interleukin-8 (IL-8) or reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for tumor necrosis factor-α (TNF-α). Hyaluronic acid (HA) secretion was determined by an ELISA. Our results show a decrease in ROS production and TNF-α expression by ME (5 µg/mL) in HaCaT under pro-oxidant and pro-inflammatory conditions, respectively. ME protected HaCaT against oxidative stress and inflammation. Our findings confirm that ME can be used for the development of bioactive compounds against epidermal damage.

Andrographis Paniculata and Its Bioactive Diterpenoids Protect Dermal Fibroblasts Against Inflammation and Oxidative Stress.

Andrographis paniculata (Burm.f.) has long been used in ayurvedic medicine through its anti-inflammatory properties. However, its protective effect of skin aging has not been studied in vitro. This study aimed to investigate the anti-aging effects of methanolic extract (ME), andrographolide (ANDRO), neoandrographolide (NEO), 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12) on human dermal fibroblasts (HDFa) under pro-oxidant or pro-inflammatory condition. The in vitro anti-aging capacity of ME, ANDRO, NEO, 14DAP, and 14DAP11-12 (1, 2.5 and 5 µg/mL) was performed in HDFa. Oxidative stress and inflammation were induced by hydrogen peroxide and lipopolysaccharide/TNF-α, respectively. Reactive oxygen species (ROS) production was measured by the fluorescence of DCF-DA probe and cytokines were quantified by ELISA (IL6 and IL8) or RTqPCR (TNF-α). Procollagen type I production was determined by an ELISA. Our results showed a decrease in ROS production with ME and 14DAP at 5 µg/mL and 1 µg/mL, respectively. Furthermore, IL-6 production and TNF-α expression decreased under ANDRO and ME at 5 µg/mL. Our data indicated that ME and 14DAP protect from oxidative stress. Additionally, ME and ANDRO decreased an inflammation marker, IL-6. This suggests their potential natural treatment against skin damage. Hence, their applications could be of interest in cosmetics for preventing skin ageing.