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BMC Complementary Medicine and Therapies Sep 2022Black salve is a controversial complementary and alternative medicine (CAM) associated with skin toxicity and skin cancer treatment failures. Black salve formulations...
BACKGROUND
Black salve is a controversial complementary and alternative medicine (CAM) associated with skin toxicity and skin cancer treatment failures. Black salve formulations vary between manufacturers and contain a number of botanical and synthetic constituents. The skin cancer cytotoxicity of a number of these constituents has not been assessed to date. The alkaloids from the rhizomes of Sanguinaria canadensis, a key black salve ingredient, have had their single compound cytotoxicity assessed; however, whether they possess synergistic cytotoxicity with other compounds has not been studied and is of direct clinical relevance. This research aimed to improve our understanding of the skin cancer cytotoxicity of black salve constituents.
METHODS
The cytotoxicity of individual and combination black salve constituents were assessed against the A375 melanoma and A431 squamous cell carcinoma cell lines. Cytotoxicity was determined using the Resazurin assay with fluorescence measured using a Tecan Infinite 200 Pro Microplate reader, compound cytotoxicity being compared to that of the topical cancer therapeutic agent, 5- fluouracil. Docetaxal was used as a positive control. Dunnetts p value was used to determine whether significant synergistic cytotoxicity was present.
RESULTS
Sanguinarine was the most cytotoxic compound tested with a 24-hour IC of 2.1 μM against the A375 Melanoma cell line and 3.14 μM against the A431 SCC cell line. All black salve constituents showed greater cytotoxicity against the two skin cancer cell lines tested than the skin cancer therapeutic 5-Fluouracil with 24 hours of compound exposure. Chelerythrine and minor Quaternary Benzophenanthridine Alkaloids (QBAs) present in black salve, at concentrations not having a cytotoxic effect by themselves, boosted the cytotoxic effects of sanguinarine. This could be a synergistic rather than additive cytotoxic effect although the synergistic effect was cell line and concentration dependent.
CONCLUSIONS
Black salve contains several cytotoxic compounds, a number of which have been found to possess synergistic cytotoxicity for the first time against skin cancer cell lines. In addition, these compounds together increase the overall cytotoxic effect. Assessing multi-compound cytotoxicity in herbal medicine can provide additional information about both their therapeutic and toxicity potential. As black salve is currently being used by patients, further cytotoxicity work should be undertaken to assess whether synergistic cytotoxicity exists when tested in normal skin cells.
Topics: Antineoplastic Agents; Benzophenanthridines; Humans; Melanoma; Ointments; Sanguinaria; Skin Neoplasms
PubMed: 36127674
DOI: 10.1186/s12906-022-03721-y -
Journal of Cosmetic Dermatology Oct 2018Keratoderma climatericum affects menopausal women, and the diagnosis relies on typical clinical findings and exclusion of other potential causes of acquired keratoderma.... (Review)
Review
Keratoderma climatericum affects menopausal women, and the diagnosis relies on typical clinical findings and exclusion of other potential causes of acquired keratoderma. Although its pathophysiology is still unknown, there has been speculation about its relation to hormonal dysregulation (possibly a local estrogen deficiency) since the 1930s. A female patient with long-lasting keratoderma climatericum was initially prescribed a topical 50% urea ointment and clobetasol propionate 0.05% ointment, with just a slight improvement after 2 months of daily use. The patient was started on topical estriol 0.125 mg/g vaginal cream applied on the plantar surface after her daily shower and application of the same topical 50% urea ointment and clobetasol propionate 0.05% ointment on alternate nights. There was a marked improvement under this regimen with total and fast control of the pruritus. At 6-month follow-up the patient retained total symptomatic control and was just applying the estriol cream and the 50% urea containing ointment. We report a case of a difficult to treat plantar keratoderma that markedly improved after adding a daily topical application of a vaginal cream containing estriol 0.125 mg/g. Trials that determine the efficacy and safety of topical estrogens for keratoderma climatericum are warranted.
Topics: Administration, Topical; Estriol; Female; Foot Dermatoses; Humans; Keratosis; Menopause; Middle Aged; Ointments; Prognosis; Severity of Illness Index; Treatment Outcome
PubMed: 28929614
DOI: 10.1111/jocd.12422 -
Yakugaku Zasshi : Journal of the... 2017Mohs paste is an external preparation containing zinc hydrochloride and zinc oxide starch as the main ingredient, and it is used for the palliative treatment of patients...
Mohs paste is an external preparation containing zinc hydrochloride and zinc oxide starch as the main ingredient, and it is used for the palliative treatment of patients with surgically untreatable malignant tumors. However, it has problems, such as changes in hardness and viscoelasticity with time and liquefaction by exudate. To overcome these problems, we modified the formulation of Mohs paste by excluding starch, which is the cause of physical changes, and investigated the base. In the modified Mohs paste using the macrogol ointment for the base, no marked change with time was noted in the hardness, malleability, or elongation property, and the water-absorbing properties were equivalent to those of Mohs paste immediately after preparation. The hardness did not decrease even after absorbing water. The drug release rate increased 1.5 times with the modified Mohs paste. Based on these findings, the risk of liquefaction-associated damage of the surrounding skin decreased on using the modified Mohs paste, and preparing in advance became possible. These results suggest that the modified Mohs paste using the macrogol ointment for the base exhibits an equivalent effect for control of exudate and a high effect for tissue fixation.
Topics: Chemical Phenomena; Chlorides; Drug Compounding; Ointment Bases; Ointments; Polyethylene Glycols; Starch; Zinc Compounds; Zinc Oxide
PubMed: 28381726
DOI: 10.1248/yakushi.16-00248 -
Mutation Research. Reviews in Mutation... Oct 2017Black salves are escharotic skin cancer therapies in clinical use since the mid 19th century. Sanguinaria canadensis, a major ingredient of black salve formulations,... (Review)
Review
Black salves are escharotic skin cancer therapies in clinical use since the mid 19th century. Sanguinaria canadensis, a major ingredient of black salve formulations, contains a number of bioactive phytochemicals including the alkaloid sanguinarine. Despite its prolonged history of clinical use, conflicting experimental results have prevented the carcinogenic potential of sanguinarine from being definitively determined. Sanguinarine has a molecular structure similar to known polyaromatic hydrocarbon carcinogens and is a DNA intercalator. Sanguinarine also generates oxidative and endoplasmic reticulum stress resulting in the unfolded protein response and the formation of 8-hydroxyguanine genetic lesions. Sanguinarine has been the subject of contradictory in vitro and in vivo genotoxicity and murine carcinogenesis test results that have delayed its carcinogenic classification. Despite this, epidemiological studies have linked mouthwash that contains sanguinarine with the development of oral leukoplakia. Sanguinarine is also proposed as an aetiological agent in gallbladder carcinoma. This literature review investigates the carcinogenic potential of sanguinarine. Reasons for contradictory genotoxicity and carcinogenesis results are explored, knowledge gaps identified and a strategy for determining the carcinogenic potential of sanguinarine especialy relating to black salve are discussed. As patients continue to apply black salve, especially to skin regions suffering from field cancerization and skin malignancies, an understanding of the genotoxic and carcinogenic potential of sanguinarine is of urgent clinical relevance.
Topics: Animals; Humans; Mouthwashes; Ointments; Phytotherapy; Plant Extracts; Sanguinaria; Skin Diseases
PubMed: 29173498
DOI: 10.1016/j.mrrev.2017.09.001 -
American Journal of Respiratory and... May 2021
Topics: Animals; Diptera; Ointments; Tuberculosis
PubMed: 33689597
DOI: 10.1164/rccm.202101-0227LE -
Journal of Ethnopharmacology Oct 2022Psoriasis, despite modern therapeutic options, is incurable and recurrent. In Unani (Greco-Arab) medicine, many medications and formulations have been prescribed by... (Randomized Controlled Trial)
Randomized Controlled Trial
ETHNOPHARMACOLOGICAL RELEVANCE
Psoriasis, despite modern therapeutic options, is incurable and recurrent. In Unani (Greco-Arab) medicine, many medications and formulations have been prescribed by eminent scholars for conditions clinically similar to psoriasis, though empirical evidence is sparse. Hence, the experimental formulations ItrīfalShāhtra and MarhamḤina were chosen to be compared to the standard therapies PUVAsol and petrolatum for their safety and efficacy.
MATERIALS AND METHODS
This open-label, randomized control clinical trial was conducted on 66 male and female participants with chronic plaque psoriasis, ranging in age from 18 to 65 years. In each group, 33 participants were block randomized to either receive Unani formulations or control drugs for 12 weeks. The Unani group received oral Itrīfal Shāhtra (a semisolid paste) and topical MarhamḤina (an ointment) twice daily, and the control group received oral 8-methoxypsoralen and topical petroleum jelly for local application. Participants of both groups were advised to get daily sunlight exposure for 5-15 min. The primary outcome measure was the change in psoriasis area and severity index (PASI) assessed at each visit. Secondary outcome measures were patient global assessment on a 100 mm VAS applied at baseline and after 12 weeks of treatment and change in subjective parameters including erythema, induration, scaling, and itching, assessed on a 5-point scale at every visit. Hemogram, LFTs, RFTs, CXR, ECG, urine, and stool tests were all assessed at baseline and after treatment for the safety of the drugs.
RESULTS
The per-protocol analysis was done on 25 participants in each group. The mean ± SD of the psoriasis area severity index (PASI) significantly decreased from 27.88 ± 12.01 and 23.61 ± 9.79 at baseline to 5.01 ± 4.59 and 9.85 ± 7.16 after completion of the trial therapies in both Unani and control groups, respectively. Also, the test formulations outperformed the control drugs on clinically significant endpoints, PASI 50 and PASI 75, with all 25 participants achieving PASI 50 and 76% achieving PASI 75.
CONCLUSION
The trial formulations, ItrīfalShāhtra and MarhamḤina may be superior to control drugs PUVAsol and petrolatum in terms of safety, efficacy, and tolerability in the treatment of chronic plaque psoriasis. Thus, the Unani formulations may further be evaluated in a well-designed multicentric superiority trial with an adequate sample size.
Topics: Adolescent; Adult; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Ointments; Petrolatum; Psoriasis; Severity of Illness Index; Treatment Outcome; Young Adult
PubMed: 35724745
DOI: 10.1016/j.jep.2022.115456 -
AAPS PharmSciTech Jul 2023Since earlier times, dermatological remedies have been utilized to treat diseases associated with pain, irritation, and skin conditions. Compared to other routes of drug... (Review)
Review
Since earlier times, dermatological remedies have been utilized to treat diseases associated with pain, irritation, and skin conditions. Compared to other routes of drug delivery, topical delivery of drugs offers several benefits. Scientists are investigating different alterations in dosage forms in addition to existing topical formulations such as ointments, gels, creams, lotions, and ointments to significantly improve the permeation of drugs and enhance the pharmacological efficacy of medications that are poorly absorbed via the skin. Conventional formulations have a plethora of problems viz. poor absorption, no target specificity, low spreadability, and inadequate bioavailability which leads the researchers toward developing novel formulations like nanoemulsions. The nanoemulsion can enhance the gradient in concentration and thermodynamic movement toward the epidermis and enhance the penetration of its constituents. However, due to its difficult application, nanoemulsion's lower viscosity limited its use in transdermal delivery. Thus, the development of nanoemulsion-based hydrogels has shown to be a successful strategy for removing obstacles from existing drug formulations. The simple application, expedient spreadability, non-stickiness, safety, and effectiveness of nanoemulsion-based hydrogel have led to substantial growth in their research in recent years. This review gives a brief idea about the prevalence of skin diseases, skin as an obstacle for drug delivery, and recent research insights to combat these obstacles. The work highlights the mechanism of drug release via nanoemulsion, hydrogels, and nanoemulsion-based hydrogels with reference to recent research on hydrophobic and hydrophilic drugs.
Topics: Hydrogels; Ointments; Drug Delivery Systems; Diffusion; Biological Availability
PubMed: 37438613
DOI: 10.1208/s12249-023-02611-x -
Supportive Care in Cancer : Official... Jun 2023Multikinase inhibitors (MKIs) treatment has been proven as a powerful strategy in cancer therapy. However, it is greatly hampered by its common adverse effect known as...
BACKGROUND
Multikinase inhibitors (MKIs) treatment has been proven as a powerful strategy in cancer therapy. However, it is greatly hampered by its common adverse effect known as hand-foot skin reaction (HFSR), especially in patients with moderate-to-severe HFSR.
OBJECTIVE
To investigate the clinical characteristics, histopathological features, treatment response, and bio-indicators of HFSR.
METHODS
We retrospectively reviewed the medical records of 102 patients with moderate-to-severe HFSR resulting from MKIs therapy.
RESULTS
The median time to development of moderate-to-severe HFSR was 18 days, which would be significantly affected by the type of MKIs and the history of HFSR. Notably, we found that HFSR was classified into three consecutive stages: erythematous lesion, yellow hyperkeratotic lesion with surrounding erythema, and hyperkeratotic lesion. Inflammation was observed in the first two stages of HFSR, but disappeared in the third stage; in contrast, the hyperkeratosis gradually became thicker from stage one to stage three. Moreover, topical medications were demonstrated as an effective therapy for HFSR, among which, the topical steroids and urea ointment treatment response rate was 37.14%, the Shouzu Ning Decoction (SND) treatment response rate was 65%, and the SND in combination with urea ointment treatment response rate was 75%, meanwhile, systemic therapies did not improve the therapeutic efficacy of topical medications alone. In addition, the serum levels of HMGB1 were found to be a potential indicator for tracking the healing process as well as predicting the prognosis of HFSR.
CONCLUSION
This study revealed the potential factors affecting the development of HFSR, evaluated the therapeutic response towards different strategies for treating HFSR, and identified a potential prognostic indicator of HFSR.
Topics: Humans; Retrospective Studies; Ointments; Protein Kinase Inhibitors; Treatment Outcome; Prognosis; Urea; Hand-Foot Syndrome; Phenylurea Compounds
PubMed: 37273007
DOI: 10.1007/s00520-023-07830-3 -
Journal of Cosmetic Dermatology Oct 2022Cheilitis is the most common mucocutaneous side effect of isotretinoin (ISO). Dexpanthenol (DXP) increases fibroblast proliferation and re-epithelialization in wound...
INTRODUCTION
Cheilitis is the most common mucocutaneous side effect of isotretinoin (ISO). Dexpanthenol (DXP) increases fibroblast proliferation and re-epithelialization in wound healing. We aimed to investigate the effect of DXP-mesotherapy in ISO-induced cheilitis in this study.
METHODS
This study was conducted on patients who had been using ISO (0.5-1 mg/kg/day) for at least 2 months. Twenty-five patients who administered DXP-mesotherapy (mesotherapy group) and 33 patients without the procedure (control group, only ointment) participated in this study. All patients were prescribed only hamamelis virginiana distillate in ointment form as a lip balm. The efficacy of the treatment was interpreted by the change in lip balm use frequency, quality of life, and Isotretinoin Cheilitis Grading Scale (ICGS).
RESULTS
There was a statistically significant decrease in all ICGS-subgroups scores in the mesotherapy group after 1 month compared with the baseline (p = <0.001), although in the controls, erythema, crust, and fissure scores significantly increased (p = 0.001, p = 0.002).While there was no difference between the groups in terms of ICGS total scores at baseline, there was a significant difference after 1 month in favor of the mesotherapy group (p < 0.001). In the mesotherapy group, lip balms were needed significantly less frequently and there was a significant improvement in quality of life compared with both the control group and at baseline after 1 month (both; p < 0.001). On the other hand, the control patients suffered more from cheilitis and dryness than at baseline (p < 0.001).
CONCLUSION
Dexpanthenol-mesotherapy seems to be a safe, and so effective method in management of ISO-related cheilitis.
Topics: Humans; Isotretinoin; Cheilitis; Mesotherapy; Ointments; Quality of Life; Lip
PubMed: 35426210
DOI: 10.1111/jocd.14993 -
Dental Materials Journal Jul 2017We investigated single application of pastes containing a surface reaction-type pre-reacted glass-ionomer (S-PRG) filler on enamel demineralization. Human enamel blocks...
We investigated single application of pastes containing a surface reaction-type pre-reacted glass-ionomer (S-PRG) filler on enamel demineralization. Human enamel blocks were polished using pastes containing S-PRG filler (0, 5, and 30%) and immersed in demineralizing solution for 5 days with daily change of solutions. The pH measurement and nanoindentation testing was carried out during the immersion period, and the enamel surfaces were examined using scanning electron microscopy and atomic force microscopy. A non-fluoride paste and a hydroxyapatite-containing paste were used for comparison. The specimens polished with the S-PRG filler-containing paste exhibited acid-neutralizing properties, which became stronger with an increasing S-PRG filler content. Following immersion in the demineralizing solution, specimens polished with the S-PRG filler-containing paste exhibited significantly greater hardness and elastic modulus values than those polished with the other pastes and exhibited a smoother surface than did the other specimens. Pastes containing S-PRG filler inhibits the demineralization of enamel.
Topics: Dental Enamel; Hardness; Humans; Microscopy, Electron, Scanning; Ointments; Tooth Demineralization; Toothpastes
PubMed: 28367912
DOI: 10.4012/dmj.2016-307