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One new seco-cyclic phorbol derivative and one new phorbol 12-monoester, named 13-oxo-14-isopropylphorbol (2), 12-angelylphorbol (5), together with four known compounds, named 4a-deoxyphorbol, 13-oxo-14-isopropenylphorbol, 12-isobutyrylphorbol, and phorbol-12-(2-methylbutyrate) were obtained by hydrolyzing croton oil. The structures of the compounds were elucidated by spectroscopic analysis. These compounds showed no cytotoxicity (CC50 > 200 μM). Phorbol-12-monoesters 4–6 showed the weak inhibitory activities on syncytia formation induced by HIV-1IIIB (4, EC50 = 56.05 μM; 5, EC50 = 72.97 μM; 6, EC50 = 52.58 μM). The seco-cyclic phorbol derivatives (2, 3) showed no anti-HIV-1 activities (EC50 > 200 μM), which indicated that chemical cleavage of cyclopropanols might affect anti-HIV-1 activity. [ABSTRACT FROM AUTHOR]

Ublituximab (BRIUMVITM), an anti-CD20 immunoglobulin G1 monoclonal antibody, is a promising new treatment option for patients with relapsing forms of multiple sclerosis (MS). Ublituximab is approved in the USA and the EU for the treatment of adult patients with relapsing forms of MS. Following a starting dose of 150 mg infused over 4 h, ublituximab is conveniently administered twice-yearly as a short (1 h) intravenous infusion. In phase 3 clinical trials in patients with relapsing MS, ublituximab was more effective than oral teriflunomide at reducing annualized relapse rates and numbers of brain lesions over a period of 96 weeks. However, ublituximab did not result in a significantly lower risk of worsening of disability. Ublituximab had an acceptable tolerability profile in clinical trials. The most commonly reported adverse events were infusion-related reactions (IRRs), which occurred in almost half of ublituximab recipients. However, the majority of IRRs were of mild to moderate severity, occurred after the first dose and decreased in frequency with subsequent dosing. Plain language summary: Multiple sclerosis (MS) is a chronic illness whereby the body's immune system causes damage to the brain and spinal cord. Most patients with MS have a relapsing-remitting form of the disease, where symptoms flare for a period of time and then ease. Ublituximab (BRIUMVITM) is a monoclonal antibody approved for treating adults with relapsing forms of MS. Of convenience to patients, ublituximab is given intravenously once every 6 months after initial dosing and can be infused rapidly (over 1 h). In clinical trials, ublituximab recipients were half as likely to have a relapse and had fewer areas of inflammation in the brain than patients receiving oral teriflunomide. However, ublituximab did not significantly reduce the risk of worsening disability. Ublituximab had an acceptable safety profile in clinical trials. Nearly half of patients receiving ublituximab had mild to moderate infusion-related reactions that became less frequent with later infusions. Thus, ublituximab is a promising new treatment option for patients with relapsing forms of MS. [ABSTRACT FROM AUTHOR]

Hemorrhoids occur due to inflammation of the rectoanal venous plexus, which causes inflammation, pain, and can cause lumps. This inflammation can cause difficulty in defecation and can even cause heavy bleeding. Empirically Tapak Liman (Elephantopus scaber) leaves have been used to treat hemorrhoids and have been known to contain flavonoids and terpenoid lactones which are active as an anti-inflammatory. Objective: To determine the anti hemorrhoidal activity of E. scaber leaves in reducing inflammation in hemorrhoids in Wistar rats. Material and method: The research begins with the extraction of E. scaber leaves with 70% ethanol as solvent. Extracts were analyzed for total flavonoid content with quercetin standard. Antihemorrhoidal activity was measured based on the degree of edema formed based on the weight of the rectum through the surgical process. Rats were induced with croton oil on the anorectal area for three days. The treatments for the test group were 50, 100, and 200 mg/kgW. The drug control group used oral diclofenac sodium for seven days. Result: E. scaber leaf ethanol extract contains alkaloids, flavonoids, saponins, and polyphenols. The flavonoid level was 3.433mgQE/g extract. This study showed that E. scaber leaf extract had the best anti hemorrhoidal activity at a dose of 100 mg/kgW with a significance value of p [ J Adv Biotechnol Exp Ther 2023; 6(2.000): 436-444]

Croton oil is liquid at room temperature, with a pale-yellow color and spicy odor. It is commonly used in combination with phenol as a chemical peeling agent in dermatology, which reveals its caustic exfoliating effects. Topical use of croton oil at a high dose produces skin irritation, inflammation, swelling, pain, and even tumors. Therefore, croton oil has been widely used for inflammation, pain, and tumor related research, with different animal models having been established. However, mechanistic studies through which croton oil induces skin swelling, injury and activates tissue repair/regeneration are limited. The present study used croton oil to induce mouse ear edema and examined tissue responses 4 h after exposure. To this end, croton oil was applied to the ventral side of mouse ears, followed by tissue collection. Samples were analyzed by hematoxylin and eosin (H&E) staining, toluidine blue staining, and immunohistochemistry staining for myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). Western blotting and ELISA were also carried out for MMP-9 together with unbiased proteomic analysis using mass-spectrometry. Results from our study demonstrated that as soon as 4 h of exposure to 2.5 % croton oil, the expression levels of MPO and MMP-9 in the dermis significantly increased compared to acetone-treated (vehicle) control ears, as did other inflammatory reactions such as swelling and neutrophil aggregation and infiltration. Subsequently, proteomic analysis confirmed that croton oil treatment resulted in significant upregulation of proteins such as myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-8 (MMP-8) in the ear skin. Interestingly, mouse ears treated with acetone vehicle showed differential expression of 2,478 proteins relative to naïve tissues; among those differentially expressed in acetone-treated samples were members of the phosphatidylinositol-glycan biosynthesis class N, T and U proteins (PIGN, PIGT, and PIGU). Overall, this work confirms the presence of neutrophil-derived MPO and MMP-9 and extends the body of knowledge to show that MMP-8 is also present during croton oil-mediated skin inflammation in the mouse ear; moreover, we find that acetone vehicle is not inert and has effects on the skin that should be considered moving forward.

Piloheal cream is an Ayurvedic proprietary medicine claimed to be effective in the treatment of hemorrhoids. The present work was undertaken to evaluate the anti-hemorrhoidal activity of Piloheal cream against croton oil-induced hemorrhoids in rats. The hemorrhoids were induced by applying 3% croton oil preparation in the anorectal region. Rats were intrarectally administered with Piloheal cream, twice a day for 4 days. Hemorrhoids were assessed by measuring macroscopic parameters such as weight, area of mucosal damage, and the number of red thrombi of anorectal tissue along with histology of the tissue. Croton oil-induced hemorrhoids were prevented by treatment with Piloheal cream as indicated by the decrease in macroscopic and histological changes in Piloheal treated rats as compared to hemorrhoids- induced rats. It is concluded that Piloheal cream exhibits a beneficial effect on croton oil-induced hemorrhoids and is useful in the treatment of hemorrhoids. [ABSTRACT FROM AUTHOR]

Teriflunomide is a drug with immunosuppressive and selective immunomodulatory action, characterized by anti-inflammatory and antiproliferative properties. Several clinical studies have demonstrated the efficacy and safety of this drug in Multiple Sclerosis, estimating a significant improvement in cognitive performance. The aim of our study is to evaluate the effects of teriflunomide by analysing the correlation between brain atrophy and the general cognitive profile and evaluating long-term changes. The effect of teriflunomide was studied in 30 patients with multiple sclerosis and 30 control subjects. Patients underwent a full cognitive profile assessment using the Brief Repeatable Battery of Neuropsychological Tests and a neuroimaging examination with a 3.0 T working scanner. Our results suggested that treatment with teriflunomide could potentially not only slow down the accumulation of microstructural tissue damage in Grey Matter and With Matter, but also better preserve the cognitive profile, particularly by highlighting the benefits in the memory domain. Thanks to drug therapy, brain volume in our patients has remained constant, leading to improvements in memory, indicating teriflunomide as a neuroprotective potential and further strengthening the evidence of a link between loss of brain volume and cognitive impairment. [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines for relapsing-remitting multiple sclerosis (RRMS) call for treatment with disease-modifying therapies (DMTs) early in the disease to prevent relapses and accumulation of neurologic impairment and disability. However, patients taking certain oral DMTs may experience gastrointestinal (GI)-related adverse events (AEs), particularly at dose titration. We conducted qualitative research with healthcare professionals (HCPs) and patients in Canada to contextualize their experiences with three oral DMTs: dimethyl fumarate (Tecfidera®), fingolimod (Gilenya®), and teriflunomide (Aubagio®). The objectives of this study were to (1) gather qualitative data to better understand the patient and HCP experience of GI AEs in oral MS DMT treatment in Canada and (2) determine to what extent two patient-reported outcome (PRO) instruments used in recent oral DMT trials capture what is important to patients regarding GI AEs in oral MS DMT treatment (content validity) and to provide qualitative data to help interpret PRO scores.Methods: This was a qualitative, non-interventional, descriptive, cross-sectional study comprising HCP and patient interviews conducted in English and French, using a 1:1 semi-structured interview approach.Results: Patients reported 16 unique GI AE concepts related to oral DMTs. The most commonly reported symptoms were diarrhea, indigestion, and nausea. While patients acknowledged the negative impact associated with GI-related AEs, most characterized the treatment experience as positive, focusing on preference for oral administration, perceived efficacy of DMTs in terms of lack of MS relapses, slowed progression of their disease, and improvement in MS symptoms. Results supported the content validity (relevance, comprehension, and comprehensiveness) of the two PROs assessed. HCP feedback reinforced patient perspectives on both GI concepts and the two PRO instruments.Conclusion: Outcomes of these research activities include experiential data on the symptom and impact experience of oral DMTs in MS from both patients and HCPs that contribute to the process of determining therapeutic value. [ABSTRACT FROM AUTHOR]

Lichenoid drug eruptions are a type of skin reaction that is caused by medication and mimics idiopathic lichen planus. Various medications have been known to cause lichenoid drug eruptions, such as antibiotics, anti-convulsants, anti-diabetics, anti-malarials, anti-tubercular drugs, anti-hypertensives, psychiatric drugs, chemotherapeutic agents, diuretics, heavy metals, and non-steroidal anti-inflammatory drugs. Various cutaneous side effects have been reported in association with teriflunomide. We present the case of a patient who developed a lichenoid eruption because of teriflunomide. The dermatologists and neurologists should be aware of these skin side effects. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) accounts for 176 cases per 100,000 inhabitants (female/male ratio = 2:1) in Italy. For most of the patients (67%), the disease course is relapsing-remitting MS (RRMS).Objective: To compare the costs and quality-adjusted life years (QALYs) of teriflunomide in RRMS naïve patients vs. RRMS patients previously treated (experienced) with other disease-modifying therapies in Italy.Methods: A four health states Markov model-supported cost-utility analysis (CUA) covering a 7-year timespan through annual cycles was developed, following the healthcare sector and the societal viewpoints. Part of the parameters that populated the Markov model was obtained from a questionnaire administered to four primary Italian MS centres. Costs of healthcare and non-healthcare resources, expressed in euro (€) 2019, and QALYs were discounted at 3% real social discount rate. One-way, scenario and probabilistic sensitivity analyses tested the uncertainty of the baseline findings.Results: Baseline CUA shows that teriflunomide in RRMS naïve patients is strongly dominant vs. experienced patients (healthcare sector perspective: - €1042.68 and + 0.480 QALYs; societal perspective: - €6782.81 and + 0.480 QALYs). Sensitivity analyses confirmed the robustness of the baseline results.Conclusion: Teriflunomide in RRMS naïve vs. experienced patients is cost-effective and possibly strongly dominant from both the healthcare sector and the society viewpoints in Italy. Our findings need further confirmation from real-world studies. [ABSTRACT FROM AUTHOR]

Phenol/croton oil is a unique chemical formulation promoting deep skin resurfacing and cellular renovation. Even though it has been used for decades in plastic surgery, the clinicopathological features, as well as the risks related to phenol/croton oil clinical application have not been thoroughly studied. The aim of the present study was to assess the effectiveness of the phenol/croton oil peel, the pathological characteristics from 1 patient at least and the emerging potential risks. A total of 64 patients were treated with phenol/croton oil peel between 2014 and 2023; in total, 21 of them underwent resurfacing at their oral area (upper/lower lips), 15 underwent resurfacing at their lower eyelid wrinkles, 22 patients underwent full face resurfacing, 2 patients were treated for their acne scars and additionally 4 patients were treated for multiple body seborrheic keratosis. The wrinkles, as well as the acne scars were markedly improved in all patients, the seborrheic keratosis was eliminated, while adverse events and undesired clinical manifestations related to peel intervention were mild and reversible for all patients. The application of phenol/croton oil constitutes an immensely powerful tool for deep chemical peeling and facial skin rejuvenation; nevertheless, it should be used cautiously due to its potential complications., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024, Spandidos Publications.)

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Background and objective: Leaves of plant Dolichandrone falcata Seem. Are traditionally used by the healers of “India” for the treatment of piles and diabetes. Therefore, the main objective of the present investigation was to evaluate the anti-hemorrhoidal potential of ethanolic leaf extract from the plant D. falcata (EDF). Methods: D. falcata leaf extract obtained after maceration process was initially subjected to phytochemical standardization with the help of HPLC using rutin as a marker compound. Hemorrhoid was induced in the rats using croton oil rat model, and the treatment was carried out with EDF suspension prepared using carboxymethyl cellulose for 5 days using 100, 200 and 300 mg/kg p. o. The scoring of inflammation was calculated on the basis of the clinical hemorrhoidal area and severity index, which was followed by estimating the level of Evans blue dye as an inflammatory marker. The hemorrhoidal tissues were also subjected to cytokine profiling, biochemical evaluation and histopathology. Results: EDF demonstrated the presence of mainly polyphenols, tannins, flavonoids, alkaloids, and saponins, while rutin was calculated to be 3.08% w/w in EDF following HPLC analysis. The results depicted more potent anti-hemorrhoidal activity of EDF at 200 mg/kg orally which was evident through the grading of inflammatory index. The result demonstrated significant decline in the levels of IL-1β, IL-6, TNF-α expression and also showed restoration of altered antioxidants and liver enzymes. Histopathological study showed minimal inflammation and reduced dilated blood vessels in treated animals, thereby confirming the tissue recovery. Conclusion: Thus, we have successfully explored and substantiated the traditional use of the leaves from the plant D. falcata for the first time in the treatment of hemorrhoids, which may be attributed to its anti-inflammatory and its antioxidant potential.

Background: Therapeutic options for children with multiple sclerosis are scarce. Teriflunomide is approved in more than 80 countries for the treatment of adults with relapsing multiple sclerosis. The TERIKIDS study examined the safety and efficacy of teriflunomide in children with relapsing multiple sclerosis.Methods: The TERIKIDS trial was a multicentre, phase 3, double-blind, parallel-group, randomised, placebo-controlled study conducted at 57 clinical centres in 22 countries in Asia, Europe, the Middle East, North Africa, and North America. The trial enrolled patients aged 10-17 years, diagnosed with relapsing multiple sclerosis and with at least one relapse in the year preceding screening or at least two relapses in the 2 years preceding screening. Patients were randomly assigned (2:1) to oral teriflunomide (dosage equivalent to 14 mg in adults) or matching placebo, using an interactive web and voice response system, for up to 96 weeks. Personnel in all sites and all patients were masked to study treatment in the double-blind period. Early entry into a subsequent 96-week open-label extension phase was possible before the end of the double-blind period for patients with confirmed clinical relapse or high MRI activity (at least five new or enlarged T2 lesions at week 24, followed by at least nine new or enlarged T2 lesions at week 36, or at least five new or enlarged T2 lesions at weeks 36 and 48, or at weeks 48 and 72). The primary endpoint was time to first confirmed clinical relapse by the end of the double-blind period. Key secondary imaging endpoints were number of new or enlarged T2 lesions and number of gadolinium-enhancing lesions per MRI scan. Efficacy endpoints were analysed in the intention-to-treat population, and safety was assessed in all patients randomly assigned to treatment and exposed to the double-blind study medication. This study is registered with ClinicalTrials.gov (trial number NCT02201108) and is closed to recruitment, but an additional optional open-label extension is ongoing.Findings: Between July 24, 2014, and the date of last patient visit on Oct 25, 2019, 185 patients were screened for eligibility, 166 (90%) were enrolled, and 109 were randomly assigned teriflunomide and 57 were randomly assigned placebo. 102 (94%) of 109 and 53 (93%) of 57 completed the double-blind period. Switch to the ongoing open-label extension because of high MRI activity was more frequent than anticipated in the placebo group (14 [13%] of 109 patients in the teriflunomide group vs 15 [26%] of 57 in the placebo group), decreasing the power of the study. After 96 weeks, there was no difference in time to first confirmed clinical relapse with teriflunomide compared with placebo (hazard ratio 0·66, 95% CI 0·39-1·11; p=0·29). Teriflunomide reduced the number of new or enlarged T2 lesions versus placebo by 55% (relative risk 0·45, 95% CI 0·29-0·71; p=0·00061), and the number of gadolinium-enhancing lesions by 75% (relative risk 0·25, 0·13-0·51; p<0·0001). Adverse events occurred in 96 (88%) patients in the teriflunomide group and 47 (82%) patients in the placebo group; serious adverse events occurred in 12 (11%) patients in the teriflunomide group and 6 (11%) patients in the placebo group. Nasopharyngitis, upper-respiratory-tract infection, alopecia, paraesthesia, abdominal pain, and increased blood creatine phosphokinase were more frequent with teriflunomide than with placebo. During the double-blind phase, four patients in the teriflunomide group had pancreatic adverse events (two with acute pancreatitis and two with pancreatic enzyme elevation), of which three events led to treatment discontinuation.Interpretation: No significant difference in time to first confirmed clinical relapse was found, possibly because more patients than expected switched from the double-blind to the open-label treatment period because of high MRI activity. Key secondary imaging analyses and a prespecified sensitivity analysis of probability of relapse or high MRI activity suggest that teriflunomide might have beneficial effects in children with relapsing multiple sclerosis by reducing the risk of focal inflammatory activity.Funding: Sanofi. [ABSTRACT FROM AUTHOR]

Croton oil is liquid at room temperature, with a pale-yellow color and spicy odor. It is commonly used in combination with phenol as a chemical peeling agent in dermatology, which reveals its caustic exfoliating effects. Topical use of croton oil at a high dose produces skin irritation, inflammation, swelling, pain, and even tumors. Therefore, croton oil has been widely used for inflammation, pain, and tumor related research, with different animal models having been established. However, mechanistic studies through which croton oil induces skin swelling, injury and activates tissue repair/regeneration are limited. The present study used croton oil to induce mouse ear edema and examined tissue responses 4 h after exposure. To this end, croton oil was applied to the ventral side of mouse ears, followed by tissue collection. Samples were analyzed by hematoxylin and eosin (H&E) staining, toluidine blue staining, and immunohistochemistry staining for myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9). Western blotting and ELISA were also carried out for MMP-9 together with unbiased proteomic analysis using mass-spectrometry. Results from our study demonstrated that as soon as 4 h of exposure to 2.5 % croton oil, the expression levels of MPO and MMP-9 in the dermis significantly increased compared to acetone-treated (vehicle) control ears, as did other inflammatory reactions such as swelling and neutrophil aggregation and infiltration. Subsequently, proteomic analysis confirmed that croton oil treatment resulted in significant upregulation of proteins such as myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and matrix metalloproteinase-8 (MMP-8) in the ear skin. Interestingly, mouse ears treated with acetone vehicle showed differential expression of 2,478 proteins relative to naïve tissues; among those differentially expressed in acetone-treated samples were members of the phosphatidylinositol-glycan biosynthesis class N, T and U proteins (PIGN, PIGT, and PIGU). Overall, this work confirms the presence of neutrophil-derived MPO and MMP-9 and extends the body of knowledge to show that MMP-8 is also present during croton oil-mediated skin inflammation in the mouse ear; moreover, we find that acetone vehicle is not inert and has effects on the skin that should be considered moving forward., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

Background: Microneedling has been shown to release growth factors, which improves the appearance of acne scars by itself and in combination with different therapy modalities. Combining microneedling with Chemical Reconstruction of Scarred Skin (CROSS) therapy using a 60% phenol and 0.2% croton oil combination results in a significant improvement of acne scarring., Objective: To assess the safety and efficacy of combination treatments using microneedling in combination with CROSS therapy that contains 60% phenol and 0.2% croton preparation in patients with Fitzpatrick skin types III to V.&nbsp; Materials and Methods: Patients were treated over a 5-year period for atrophic acne scars using microneedling combined with CROSS. Most of the patients had combination atrophic scarring. High-quality before and after photographs were taken of the patients to assess the improvement in the scars.&nbsp; Results: Most of the patients (89.5%) had Fitzpatrick skin types IV through V.&nbsp; Analysis was done on a maximum of 3 microneedling sessions with 1 to 3 CROSS sessions. Photographic evaluation using the Global Aesthetic Improvement Scale showed an 18% grade-1 improvement and 81% grade-2 improvement. The Goodman and Baron Qualitative scar grading system showed a 62% grade-1 improvement and 38% grade-2 improvement., Conclusion: Combination treatments work best for atrophic scars. This is the first published report of using microneedling with a 60% phenol/0.2% croton oil combination. It proved to be very effective and safe in treating atrophic acne scars in Fitzpatrick skin types III to V, with minimal side effects and a quick recovery. J Drugs Dermatol. 2024;23(6):418-422.&nbsp; &nbsp;&nbsp; doi:10.36849/JDD.7657.

Ethnopharmacological Relevance: Ammodaucus leucotrichus Coss. & Durieu (Apiaceae) is traditionally used in southern Algeria as a remedy against a wide range of disease due to its health-promoting properties., Aim of the Study: To investigate anti-oxidant and anti-inflammatory potentials of plant methanolic extract and its fractions in vitro and in vivo., Materials and Methods: Anti-radical activity was assessed in vitro using ABTS •+ , superoxide anion (O 2 •- NO). Lipid peroxidation inhibition was also investigated in the linoleic acid system. Enzyme inhibition assay was performed against α-amylase and α-glucosidase. The anti-inflammatory effect of extracts was screened in vitro through thermal induction of human serum albumin, and in vivo on a skin acute inflammation model induced by λ-carrageenan paw injection, xylene and croton oil topical application. Analgesic effect was evaluated by acetic acid-induced writhing test.• NO). Lipid peroxidation inhibition was also investigated in the linoleic acid system. Enzyme inhibition assay was performed against α-amylase and α-glucosidase. The anti-inflammatory effect of extracts was screened in vitro through thermal induction of human serum albumin, and in vivo on a skin acute inflammation model induced by λ-carrageenan paw injection, xylene and croton oil topical application. Analgesic effect was evaluated by acetic acid-induced writhing test., Results: The highest contents of polyphenols and flavonoids was recorded by the crude extract (77.14 ± 0.01 μg GAE/mg E and 19.59 ± 0.08 μg QE/mg E, respectively). Among the extracts, ethyl acetate extract showed a promising anti-radical activity of ABTS •+ , O 2 •- NO, in addition to a remarkable inhibition activity of the tested enzymes. Meanwhile, all extracts effectively protected linoleic acid against lipid peroxidation and human serum albumin structure in thermal condition even at low concentration (0.31 mg/ml). Oral administration of 200 mg/kg of crude extract successfully inhibited acetic acid induced nociception and reduced edema formation induced by xylene and carrageenan. However, a dose-dependent manner was observed to decrease ear edema by a microscopic examination in croton oil induced acute inflammation. Nitrite and malondialdehyde levels together with catalase activity were modulated in the presence of plant-derived bioactive compounds.• NO, in addition to a remarkable inhibition activity of the tested enzymes. Meanwhile, all extracts effectively protected linoleic acid against lipid peroxidation and human serum albumin structure in thermal condition even at low concentration (0.31 mg/ml). Oral administration of 200 mg/kg of crude extract successfully inhibited acetic acid induced nociception and reduced edema formation induced by xylene and carrageenan. However, a dose-dependent manner was observed to decrease ear edema by a microscopic examination in croton oil induced acute inflammation. Nitrite and malondialdehyde levels together with catalase activity were modulated in the presence of plant-derived bioactive compounds., Conclusions: This study showed that Ammodaucus leucotrichus is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nowadays, there is a growing interest in the development of medicinal plant-based therapies to diminish the ravages of the inflammatory process related to diseases and tissue damage. Most therapeutic effects of these traditional medicinal plants are owed to their phenolic and antioxidant properties. C. aconitifolius is a traditional medicinal plant in Mexico. Previous characterization reports have stated its high nutritional and antioxidant components. The present study aimed to better understand the biological activity of C. aconitifolius in inflammation response. We developed an ethyl acetate extract of this plant to evaluate its anti-inflammatory capacity and its flavonoid content. The topical anti-inflammatory effect of the ethyl acetate extract of C. aconitifolius was determined by the croton oil-induced mouse ear edema test, while flavonoid detection and concentration were determined by thin layer chromatography and the aluminum chloride colorimetric assay, respectively. Topical application of the extract showed significant inhibition of the induced-ear edema (23.52 and 49.41% for 25 and 50 mg/kg dose, respectively). The extract also exhibited the presence of flavonoids. The finding of the anti-inflammatory activity exerted by the C. aconitifolius and the identification of its active principles may suggest and support its use for inflammation treatment. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinases (CDKs) serve as target for various cancers including skin cancer. Secoisolariciresinoldiglucoside (SDG) and lignans exert anticancer effect on colon cancer through inhibition of CDKs. However, reports of SDG lignan concentrate (SLC) of Linum usitatissimum (L.) on skin cancer are not available. Hence, in this study, we evaluated the effect of SLC of L. usitatissimum on skin cancer, and determined the mechanism of action. Cell viability studies were done using the A-375 cell line. Skin cancer was induced by dimethyl Benz(a) anthracene and croton oil in female balb/c mice. SLC (5%) was administered from the 7th to 16th week after which we evaluated serum and tissue parameters. The IC50 value of SLC was found to be 93.7 µg/mL on the A-375 cell line. Skin cancer control animals exhibited increased tumor volume and burden and an increase in non-specific serum markers and tissue markers. Treatment with SLC decreased tumor volume and burden, and serum and tissue markers. Histopathological studies also depicted protection with SLC treatment. Docking studies revealed that SDG exhibits a good binding score with CDK4. Skin cancer control mice showed significantly increased CDK4 mRNA and decreased p53 mRNA levels which were prevented by SLC treatment. SLC exhibited a chemopreventive effect in skin cancer depicted by a reduction in serum biomarker, oxidative stress, collagen levels, tumor volume, tumor burden, and histopathological studies. These effects are mediated through the inhibition of CDK4 and upregulation of p53. [ABSTRACT FROM AUTHOR]

A new ent-kaurane-type diterpenoid, crotonmekongenin A (1) together with two known compounds, epifriedelanol (2) and sitosterol glucoside (3) from the leaves and twigs of Croton mekongensis were isolated. The structure of these compounds was determined by spectroscopic analysis. The structure of the new ent-kaurane-type diterpenoid (1) was elucidated using spectroscopic technique and X-ray crystallography analysis. Moreover, the cytotoxicity of all extract and isolated compounds was tested for cytotoxicity against KKU-M213, FaDu, HT-29, MDA-MB-231, A-549, SH-SY5Y, and CL cell lines. Compound 1 showed significant cytotoxic activity (ED50) on FaDu (0.48 µg/ml), HT-29 (0.63 µg/ml), and SH-SY5Y (0.45 µg/ml). [ABSTRACT FROM AUTHOR]

Objective: Leflunomide is a commonly used disease-modifying drug in the treatment of rheumatoid arthritis (RA). Its effects are mediated via inhibition of dihydroorotate dehydrogenase (DHODH) by its active metabolite teriflunomide, and the pharmacokinetics of teriflunomide are highly variable. Our objective was to examine the association between the DHODH haplotype and plasma teriflunomide concentration with response to leflunomide in patients with RA where leflunomide was added to an existing disease-modifying drug regimen after failure to achieve an adequate response with conventional triple therapy.Methods: Patients with RA who were taking, or were about to initiate, leflunomide were included. Participant characteristics, including the DHODH haplotype, were determined. Up to 5 plasma samples were collected after leflunomide was initiated for assays of total and free teriflunomide concentration. Disease activity was determined via the 28-joint Disease Activity Score (DAS28). The association between DAS28 scores and patient covariates was determined by linear mixed-effects modeling.Results: A total of 67 patients were included in the study. The DAS28 score after initiation of leflunomide was associated with the baseline DAS28 score (β = 0.70, P < 0.001) and was higher in those who carried the DHODH haplotype 2 (β = 0.56. P = 0.01) and did not carry the shared epitope (β = 0.56, P = 0.013). As total and free plasma teriflunomide concentration increased, the DAS28 score was significantly lower (P < 0.001 and P = 0.001, respectively). When considering threshold concentrations, teriflunomide concentrations >16 mg/liter were associated with a DAS28 score that was 0.33 lower, and when free teriflunomide concentration was >35 µg/liter, the DAS28 score was 0.32 lower.Conclusion: Teriflunomide concentration and carriage of the DHODH haplotype 2 are associated with response to leflunomide in patients with RA, and a total plasma teriflunomide concentration of at least 16 mg/liter is needed to maximize the likelihood of response. [ABSTRACT FROM AUTHOR]

Background: The fruits of Apiaceae family have been widely used in traditional medicine for the treatment of pain and inflammation. In this study, we evaluated the analgesic and anti-inflammatory effects of wild celery (Smyrniopsis aucheri) seeds, as a member of the Apiaceae family. Methods: Hydroalcoholic and hexane extracts of seeds were prepared and for the evaluation of analgesic activity, acetic acid, formalin, and hotplate tests in male mice (20-30 g) and for anti-inflammatory assessment carrageenan-induced paw edema in rats and croton oil-induced ear edema in mice were used. Results: Hydroalcoholic and hexane extracts (100-400 mg/kg) significantly reduced abdominal spasms in the acetic acid test. In the formalin test, the hydroalcoholic extract at doses of 200 and 400 mg/kg reduced the pain of the chronic phase while hexane extract was effective in both acute and chronic phases. In the hot plate test, both extracts were ineffective. In the carrageenan and croton tests, both extracts at a dose of 400 mg/kg significantly reduced edema. Conclusions: The results revealed the analgesic and anti-inflammatory effects of plant seed extracts. Due to the lack of response of the extracts in the hot plate test, it seems that the plant mainly has a peripheral analgesic effect. [ABSTRACT FROM AUTHOR]

Background : The 1st and 2nd degree hemorrhoids is managed non-operatively with the anti-inflammatory and plebothropic drugs. Graptophyllum pictum extract (GPE) has already been used widely in Indonesia to treat hemorrhoid with good result, however, the mechanism is not supported by the molecular research. Objective : This study is intended to study the phlebothropic effects of GPE by measuring the degree of edema and extravassal leucocytes of experimental wistar hemorrhoid. Methods : Experimental study with Randomized Controlled Trial Post-test only design in male wistar rats, weight around 200 gr, induced for the development of a disease-like condition of hemorrhoids by 6% croton oil on the anus for 3 days. Random allocation was performed to divide the 14 wistar rats in 2 groups. Group I as control got normal saline solution, while group II was treated with GPE 100mg/kgbw, started on day 4th for 5 consecutive days. On 9th day blood was extracted from retroorbital fossa and anus was resected up to 2 cm from anal verge and weighted. The degree of anal edema was measured by rectoanal coefficient, that is rasio between anal weight (miligrams) and body weight (grams). Results : Until the end of study, all wistar rat were still alive. The mean (±SD) of body weight of control group was 173.84 ­(±13.37) and the treatment group was 171.70 (±13.10), and there was no significant differences (p = 0.833). The mean (±SD) of rectoanal coefficient in the treatment group was 2.46 (±0.41) and it was significantly lower than control group (3.13 ± 0.85) (p = 0.029). The mean (±SD) of extravassal leukocytes in the treatment group was 900.14(±48.09) and it was significantly lower than the control (1003.28 ± 99.30) (p = 0.042). Conclusions : Graptophyllum pictum extract at doses of 100 mg/Kgbw have phlebotonic effect in decreased edema and extravassal leukocytes.

Ethnopharmacological relevance: Tabernaemontana catharinensis, popularly known as snakeskin, is used in traditional medicine to treat skin inflammatory disorders. To confirm the topical anti-inflammatory effect of T. catharinensis leaves, we evaluated the therapeutic effect of crude extract (TcE) and its different fractions on irritant contact dermatitis model in mice and verified its anti-inflammatory action mechanism. Materials and methods: The qualitative phytochemical analysis of TcE and its dichloromethane, n-butanol and ethyl acetate fractions was performed by UHPLC-ESI-HRMS. The gel accelerated stability was performed to ensure the effectiveness formulation. We investigated the TcE’ inhibitory effect, its fractions and a gel formulation containing TcE in irritant contact dermatitis models induced by unique (1000 μg/ear) and multiple (400 μg/ear) croton oil application, evaluated by the ear edema formation, inflammatory cell infiltration (MPO activity measurement and histological procedure) and pro-inflammatory cytokines levels. The action glucocorticoid-like of TcE was investigated using a glucocorticoid receptor antagonist (mifepristone; 50 mg/kg, s.c.). Results: The treatments (10 μg/ear) reduced the ear edema and MPO activity by 100% and 94 ± 3% (TcE) 85 ± 4% and 88 ± 3% (dichloromethane fraction), 83 ± 6% and 73 ± 11% (n-butanol fraction) and 86 ± 6% and 93 ± 4% (ethyl acetate fraction) and 100% (dexamethasone solution), respectively to the acute ICD model. The TcE and dexamethasone gel (15 mg/ear) also reduced by 66 ± 6% and 70 ± 5% the ear edema and by 58 ± 14% and 84 ± 4% the MPO activity, respectively. To the chronic ICD model, the TcE and dexamethasone (10 μg/ear) also reduced the ear edema (66 ± 6% and 70 ± 5%) and the MPO activity (58 ± 14% and 84 ± 4%); on the 9th day of the experiment. TcE and dexamethasone also reduced the pro-inflammatory cytokines (MIP-2, IL-1β and TNF-α) levels in acute ICD model induced by croton oil. Besides, mifepristone prevented the topical anti-edematogenic effect of TcE’ and dexamethasone’ solutions by 97 ± 9% to TcE and 75 ± 15% to dexamethasone. The accelerated stability study of T.catharinensis gels showed no relevant changes at low temperatures. The dereplication of the TcE and fractions revealed the presence of indole alkaloids, triterpenes, and flavonoids by UHPLC-ESI-HRMS. These classes of compounds are known in the literature for present potential anti-inflammatory action, supporting the results obtained. Conclusion: The results confirm the topical popular use ofT.catharinensis leaves in the treatment of skin inflammation and demonstrate the TcE’ potential for the development of a promising topical anti-inflammatory agent to treat inflammatory disorders.

Abstract Inflammatory dermatoses are prevalent worldwide, with impacts on the quality of life of patients and their families. The aim of this study was to determine the anti-inflammatory effects of Achyrocline satureioides oily extracts and nanocapsules on the skin using a mouse model of irritant contact dermatitis induced by croton oil, and a skin inflammation model induced by ultraviolet B (UVB) radiation. The mice were treated with 15 mg/ear oily extract (HG-OLAS) or nanocapsules (HG-NCAS) of A. satureioides incorporated into Carbopol® 940 hydrogels. We found that HG-OLAS and HG-NCAS formulations reduced ear edema in croton oil-induced lesions with maximum inhibitions of 54±7% and 74±3%, respectively. HG-OLAS and HG-NCAS formulations decreased ear edema induced by UVB radiation (0.5 J/cm2), with maximum inhibitions of 68±6% and 76±2% compared to the UVB radiation group, respectively. HG-OLAS and HG-NCAS modulated myeloperoxidase (MPO) activity after croton oil induction. Furthermore, croton oil and UVB radiation for 6 and 24 h, respectively, stimulated polymorphonuclear cells infiltration. The topical treatments reduced inflammatory processes, as shown by histological analysis. Together, the data suggest that topical application of A. satureioides oily extracts and nanocapsules produced antiedematogenic and anti-inflammatory effects. They constitute a compelling alternative for treatment of skin injuries.

The sesquiterpene β-caryophyllene, classified as a phytocannabinoid compound, has been widely studied owing to its multi-target action. In addition, this compound has demonstrated application as a skin permeation promoter. In this context, this study aimed to evaluate the feasibility of associating β-caryophyllene and indomethacin in the oily core of hydrogel thickened nanoemulsions, as well as, to evaluate the in vivo anti-inflammatory effect of this association by croton oil ear edoema induced model. After topical application, the nanoemulgels resulted in increased edoema mass when compared to the substances in their free form. Overall, the results differed from expected, and the data found may be owing to the specificities of the in vivo model applied, as well as the tested ratio between β-caryophyllene and indomethacin (200:1). New perspectives arise from the data found regarding the evaluation of the association of terpenic compounds with indomethacin in nanoemulsified systems.

What is know and objective: Teriflunomide is indicated for the treatment of adult patients with relapsing‐remitting multiple sclerosis. Case summary: We present a rare intoxication with a high dose (672 mg) of teriflunomide. According to its product label, the only known treatment is the administration of colestyramine and activated carbon (charcoal). No serious adverse events occurred during the time the patient was admitted (<24 h). No long‐term overdose‐related symptoms or complaints were reported. What is new and conclusion: The fact that after the acute overdose both adverse events and laboratory parameters were acceptable, prescribing colestyramine and activated carbon, as well as monitoring of laboratory parameters such as full blood count, liver and kidney values and QTc, seems sufficient during the early stage (<24 h after intake) of teriflunomide overdose. [ABSTRACT FROM AUTHOR]

Background: Hemorrhoids are rectoanal venous plexus swelling that causes inflammation, pain, and bleeding. Plants with phenolic compounds are known to improve venous tone and anti-inflammation. Soursop leaves (Annona muricata L.) known contain phenolic compounds and have been used to cure inflammation. However, studies on anti-inflammatory soursop leaves for hemorrhoids are still limited. Objective: This study aims to analyze the effect of Soursop Leaves Ethanol Extract (SLEE) on the histopathological features and expression of COX-2 and TNFa in rectoanal tissue. Method: Swiss mice 20 weeks induced 3 times with 6% croton oil through the anus. SLEE doses of 100, 200, and 400 mg/Kg and aspirin as a positive control were given orally for 7 days. Histopathological examination of the rectoanal tissue of mice was assessed by counting cell necrosis, inflammation, vasodilation, and edema using hematoxylin-eosin. Positive cells expressing COX-2 and TNFa were counted on inflammatory epithelial cells using immunohistochemistry. Results: Administration of SLEE at all doses showed different levels of inflammation, necrosis, vasodilatation and edema in histopathology of rectoanal tissue P <0.00. All three doses of SLEE show significant anti-inflammatory effects on hemorrhoidal tissue. SLEE doses of 200, 400 mg/Kg significantly decreased COX-2 P <0.05 compared to negative controls, and SLEE doses of 100, 200, and 400 mg/Kg significantly decreased TNFa P <0.05 compared to negative controls. Conclusions: SLEE can reduce inflammation and has the potential to be developed as a natural remedy for hemorrhoids. [ABSTRACT FROM AUTHOR]

The treatment of cutaneous inflammation with topical corticosteroids may cause adverse effects reinforcing the need for therapeutic alternatives to treat inflammatory skin disorders. We investigated the anti-inflammatory effect of oleic acid (OA), a fatty acid of the omega-9 (ω-9) family, and we point out it as an alternative to treat inflammatory skin disorders. OA was incorporated into Lanette®- or Pemulen® TR2-based semisolid preparations and the pH, spreadability, rheological behavior and in vivo anti-inflammatory performance in a UVB radiation-induced skin inflammation model in mice were assessed. The anti-inflammatory activity was verified after single or repeated treatment of the mouse ear following the UVB. The OA action on glucocorticoid receptors was investigated. Both semisolids presented pH values compatible with the deeper skin layers, appropriate spreadability factors, and non-Newtonian pseudoplastic rheological behavior. Pemulen® 3% OA inhibited ear edema with superior efficacy than Lanette® 3% OA and dexamethasone after a single treatment. Pemulen® 3% OA and dexamethasone also reduced inflammatory cell infiltration. After repeated treatments, all formulations decreased the ear edema at 24 h, 48 h and 72 h after UVB. OA in semisolids, especially Pemulen® TR2-based ones, presented suitable characteristics for cutaneous administration and its anti-inflammatory activity seems to occur via glucocorticoid receptors. OA was also capable to reduce croton oil-induced skin inflammation. Besides, the ex vivo skin permeation study indicated that OA reaches the receptor medium, which correlates with a systemic absorption in vivo. The natural compound OA could represent a promising alternative to those available to treat inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

Objective: Disease modifying therapies (DMTs) for multiple sclerosis (MS) aim to delay progression and reduce relapses. Evidence is limited on the comparative effectiveness of the oral DMTs fingolimod and teriflunomide. This study evaluated time to treatment failure among patients with MS who initiated fingolimod versus teriflunomide in real-world settings.Methods: The retrospective cohort included 18-64 year old patients diagnosed with MS who initiated fingolimod or teriflunomide during 12 September 2012 to 30 September 2015 within MarketScan Commercial and Medicare Claims. Patients were followed from treatment initiation (index date) until first treatment failure or censoring. Treatment failure was defined as the first occurrence of MS relapse (identified using a validated algorithm) or treatment discontinuation (≥60 day supply gap). Treatment failure was examined through Kaplan-Meier analysis and multivariable Cox regression adjusting for 1 year baseline factors (age, gender, plan type, region, index year, prior DMT use, baseline relapses, Charlson Comorbidity Index [CCI] and MS symptoms).Results: On average, patients treated with fingolimod (n = 2704) were younger (43.6 versus 49.8 years) with lower CCI (0.4 versus 0.7) and more relapses at baseline (0.46 versus 0.42) than those treated with teriflunomide (n = 1859). Median time to treatment failure was 19.5 months with fingolimod versus 9.6 months with teriflunomide (p < .001). After controlling key demographic and clinical characteristics through multivariable regression, fingolimod was associated with 38.9% lower hazards of treatment failure versus teriflunomide (adjusted hazard ratio = 0.611; 95% CI: 0.559-0.669; p < .001).Conclusions: In a large cohort of US adults with MS, controlling for key baseline characteristics, fingolimod was associated with significantly longer time to treatment failure and lower risk of treatment failure compared with teriflunomide. [ABSTRACT FROM AUTHOR]

Background: The multi-drug resistance transporter ABCG2, a member of the ATP-binding cassette (ABC) transporter family, mediates the efflux of different immunotherapeutics used in multiple sclerosis (MS), e.g., teriflunomide (teri), cladribine, and mitoxantrone, across cell membranes and organelles. Hence, the modulation of ABCG2 activity could have potential therapeutic implications in MS. In this study, we aimed at investigating the functional impact of abcg2 modulation on teri-induced effects in vitro and in vivo.Methods: T cells from C57BL/6 J wild-type (wt) and abcg2-knockout (KO) mice were treated with teri at different concentrations with/without specific abcg2-inhibitors (Ko143; Fumitremorgin C) and analyzed for intracellular teri concentration (HPLC; LS-MS/MS), T cell apoptosis (annexin V/PI), and proliferation (CSFE). Experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6J by active immunization with MOG35-55/CFA. Teri (10 mg/kg body weight) was given orally once daily after individual disease onset. abcg2-mRNA expression (spinal cord, splenic T cells) was analyzed using qRT-PCR.Results: In vitro, intracellular teri concentration in T cells was 2.5-fold higher in abcg2-KO mice than in wt mice. Teri-induced inhibition of T cell proliferation was two fold increased in abcg2-KO cells compared to wt cells. T cell apoptosis demonstrated analogous results with 3.1-fold increased apoptosis after pharmacological abcg2-inhibition in wt cells. abcg2-mRNA was differentially regulated during different phases of EAE within the central nervous system and peripheral organs. In vivo, at a dosage not efficacious in wt animals, teri treatment ameliorated clinical EAE in abcg2-KO mice which was accompanied by higher spinal cord tissue concentrations of teri.Conclusion: Functional relevance of abcg2 modulation on teri effects in vitro and in vivo warrants further investigation as a potential determinant of interindividual treatment response in MS, with potential implications for other immunotherapies. [ABSTRACT FROM AUTHOR]

Several species from Maytenus genus (Celastraceae family) show anti-inflammatory activity associated to terpene presence. Thus we intend to isolate and characterize triterpenes having potential anti-inflammatory activity from the bark of Maytenus elaeodendroides Griseb. Isolation, purification and structural elucidation of such compounds were achieved by maceration with petroleum ether/diethyl ether (1:1), followed by chromatographic and spectroscopic methods. Anti-inflammatory activity was evaluated by inhibition of Croton oil- induced ear edema in mice. The triterpenes isolated were: 28-hydroxy-3-oxo-20(29)-lupene, 16-hydroxy-3-oxo-20(29)- lupene (herein found for the first time in the Celastraceae family), 3dihydroxy-20(29)-lupene and acid 3-oxo-20(29)-lupene-28-oic. At certain doses the obtained extract showed an antiinflammatory effect as potent as that exhibited by diclofenac (reference drug). This is the first time it is reported an anti-inflammatory activity for 16-hydroxy-3-oxo-20(29)-lupene. An increase in the anti-inflammatory activity of this last terpene is probably related to the presence of carbonile group in C-3. [ABSTRACT FROM AUTHOR]

Sanhuang ointment (SHO) has been widely used in the traditional Chinese medical system for 1500 years and has efficacy in clearing away heat and dampness, reducing swelling, and alleviating pain. Hemorrhoids will damage the normal physiological function of the body, resulting in obstructed defecation, accompanied by massive hemorrhage and necrosis of tissues and cells, which is easy to breed bacteria and cause infection. SHO can promote lesion healing in hemorrhoid rats, but the pharmacological mechanism underlying this effect remains unknown. To evaluate the effect of SHO on experimental hemorrhoids in rats induced by croton oil and glacial acetic acid. In this research, the effective components of SHO were analyzed in detail by High performance liquid chromatography (HPLC) and Liquid chromatography/mass spectrometry (LC/MS). Hemorrhoids were induced by 6% balsam and glacial acetic acid respectively in the anorectal region of rats. SHO was administered externally to the anorectal region of rats at doses of 185 mg/g (crude drug/ointment), 370 mg/g (crude drug/ointment) and 740 mg/g (crude drug/ointment) for 11 days. Mayinglong musk hemorrhoids ointment (1 g/kg) and Taining cream (1 g/kg) were used as reference anti hemorrhoids drugs. On the 11th day, hemorrhoids were evaluated by measuring the biochemical parameters of hemorrhoids in rats and the histology of anorectal tissues. Using high performance liquid chromatography liquid chromatography mass spectrometry, 41 compounds, including phenylpropionic acids and alkaloids, were identified. the fingerprints of 18 common peaks were identified. In Hemorrhoids like rats, acetic acid induced inflammation was inhibited in a dose-dependent manner during SHO treatment. In addition, the detailed experimental results show that SHO can effectively improve hemorrhoids by inhibiting the production of inflammatory cytokines in serum, reversing the down-regulation of vanillin subtype 1 (TRPV1), calcitonin gene related peptide (CGRP) and substance P (SP) levels of pain related genes in anal tissues, and the up regulation of Vascular endothelial growth factor (VEGF) levels of vascular growth related genes. The results showed that SHO could alleviate the edema caused by the exudation of anorectal tissue fluid in rats by anti-inflammatory effect and reducing the Vascular permeability of rats. The study validates the traditional use of SHO in the treatment of hemorrhoids and demonstrates its anti-hemorrhoidal potential. [Display omitted] [ABSTRACT FROM AUTHOR]

Nowadays, there is a growing interest in the development of medicinal plant-based therapies to diminish the ravages of the inflammatory process related to diseases and tissue damage. Most therapeutic effects of these traditional medicinal plants are owed to their phenolic and antioxidant properties. C. aconitifolius is a traditional medicinal plant in Mexico. Previous characterization reports have stated its high nutritional and antioxidant components. The present study aimed to better understand the biological activity of C. aconitifolius in inflammation response. We developed an ethyl acetate extract of this plant to evaluate its anti-inflammatory capacity and its flavonoid content. The topical anti-inflammatory effect of the ethyl acetate extract of C. aconitifolius was determined by the croton oil-induced mouse ear edema test, while flavonoid detection and concentration were determined by thin layer chromatography and the aluminum chloride colorimetric assay, respectively. Topical application of the extract showed significant inhibition of the induced-ear edema (23.52 and 49.41% for 25 and 50 mg/kg dose, respectively). The extract also exhibited the presence of flavonoids. The finding of the anti-inflammatory activity exerted by the C. aconitifolius and the identification of its active principles may suggest and support its use for inflammation treatment.

Background: Croton oil is the only commercial source of the diterpenoid phorbol (1a), the starting material for the semi-synthesis of various diesters extensively used in biomedical research to investigate cell function and to evaluate in vivo anti-inflammatory activity. While efficient chemoselective esterification protocols have been developed for phorbol, its isolation from croton oil is technically complicated, and involves extensive manipulation of very toxic materials like the oil or its native diterpenoid fraction.Results: The preparation of a crude non-irritant phorboid mixture from croton oil was telescoped to only five operational steps, and phorbol could then be purified by gravity column chromatography and crystallization. Evidence is provided that two distinct phorboid chemotypes of croton oil exist, differing in the relative proportion of type-A and type-B esters and showing different stability to deacylation.Conclusion: The isolation of phorbol from croton oil is dangerous because of the toxic properties of the oil, poorly reproducible because of differences in its phorboid profile, and time-consuming because of the capricious final crystallization step. A solution for these issues is provided, suggesting that the poor-reproducibility of croton oil-based anti-inflammatory assays are the result of poor quality and/or inconsistent composition of croton oil.

Ethnopharmacological Relevance: Cistus laurifolius is widely used in folk medicine in Anatolia for the treatment of many ailments. The leaves of the plant are used in the form of tea in the treatment of hemorrhoids in the Western Black Sea Region and Central Anatolia., Aims of the Study: It was aimed at evaluating the anti-hemorrhoidal effects of C. laurifolus leaves in croton oil-induced hemorrhoid model in rats., Materials and Methods: The methanolic and aqueous extracts of C. laurifolius were tested for in vivo anti-hemorrhoidal efficacy using an experimental hemorrhoid model, followed by histological and biochemical analysis. Hemorrhoid was created by using croton oil on the anal region of the rats. TNF-α and VEGF mRNA expression levels were assessed using real-time PCR detections. The extract was also tested for anti-inflammatory properties, which are based on the suppression of an increase in capillary permeability caused by acetic acid. LC-QTOF-MS and RP-HPLC were used for the phytochemical analysis., Results: In comparison to the control, histological and biochemical assessment showed that the methanolic extract of C. laurifolius is particularly effective against hemorrhoids. The same extract group's TNF-α mRNA expression was found to be the lowest. Additionally, the methanolic extract showed a strong inhibitory effect on the increase in capillary permeability resulted on by acetic acid. Three phenolic compounds were discovered in the extracts by phytochemical analyses, while more than eighteen compounds were found by LC-QTOF-MS analysis. Five of these compounds are phenolic acid derivatives, and flavonoids constitute the majority of the group., Conclusion: This is the first evidence from the research that C. laurifolius possesses strong anti-inflammatory and anti-hemorrhoidal properties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Facial resurfacing is a fundamental part of rejuvenation but it is often ignored because of the perceived difficulty. Lasers are an option, but they have proved inadequate for difficult rhytids (ie, perioral) both in quality and longevity. Croton oil peels can give excellent results with remarkable permanence. The misconception of danger and difficulty will be dispelled and the reality that these peels can be done in a controlled fashion and are within the grasp of any practitioner will be discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Once considered the standard for deep facial resurfacing, the classical Baker-Gordon phenol-croton oil peel has largely been replaced by formulas with lower concentrations of phenol and croton oil. The improved safety profile of deep peels has ushered in a new era in chemical peeling. Wrinkles can be improved and skin can be tightened with more subtle and natural results. No longer does a deep peel denote "alabaster white" facial depigmentation with complete effacement of wrinkles. Gregory Hetter's research showed that the strength and corresponding depth of penetration of the phenol-croton oil peel can be modified by varying the concentration of croton oil. This second article in this continuing medical education series focuses on the main historical, scientific, and procedural considerations in phenol-croton oil peels. [ABSTRACT FROM AUTHOR]