LRP1/CD91 is highly expressed in monocytes from patients with vitiligo - even after repigmentation.

Vitiligo pathophysiology is mediated by antigen-specific cytotoxic T cells. Environmental stressors cause susceptible melanocytes to secrete damage-associated molecular patterns (DAMPs). DAMPs are recognized by receptors such as the endocytic low-density lipoprotein receptor-related protein (LRP1/CD91), expressed in antigen-presenting cells, which activate self-reactive CD8+ T cells, leading to melanocyte destruction. Within this response, interferon gamma triggers production of cytokine CXCL10, recruiting more activated T cells causing further melanocytic damage. We hypothesized that expression of LRP1/CD91 was higher in vitiligo patients compared to non-vitiligo individuals. And further that levels/expression of CXCL10 in plasma were linked to disease severity. We enrolled forty individuals in this study: 18 patients with vitiligo and 22 healthy volunteers. We assessed LRP1/CD91 expression and plasma CXCL10 in patients with vitiligo and healthy volunteers. Additionally, vitiligo patients received combined treatment for 16 weeks following which the said parameters were reassessed. Vitiligo Area Scoring Index was calculated before and after treatment for these patients. Analysis of LRP1/CD91 MFI values in monocytes from vitiligo patients showed high surface levels of LRP1/CD91 than from healthy volunteers (10.50 ± 0.77 vs. 6.55 ± 0.77 MFI units, p < 0.001). This expression did not change after treatment. Plasma levels of CXCL10 were higher in vitiligo patients than healthy volunteers (93.78 ± 7.73 vs. 40.17 ± 6.25 pg/ml). The patients with a good clinical response to treatment had a parallel reduction in plasma CXCL10 levels (105.8 ± 18.44 vs. 66.13 ± 4.87 pg/ml) before and after treatment. LRP1/CD91 expression may reflect susceptibility to vitiligo. Plasma levels of CXCL10 can represent a biomarker for monitoring treatment response. LRP1 and CXCL10 may represent therapeutic targets.

Visnagin attenuates acute pancreatitis via Nrf2/NFκB pathway and abrogates associated multiple organ dysfunction.

Acute pancreatitis (AP) is an exocrine dysfunction of the pancreas where oxidative stress and inflammatory cytokines play a key role in induction and progression of the disease. Studies have demonstrated that antioxidant phytochemicals have been effective in improving pancreatitis condition, but there are no clinically approved drugs till date. Our study aims to assess the preventive activity of visnagin, a novel phytochemical isolated from Ammi visnaga against cerulein induced AP. Male Swiss albino mice were divided into six groups (n = 6, each group) comprising of normal control, cerulein control, seven day pre-treatment with visnagin at three dose levels; visnagin low dose (10 mg/kg), visnagin mid dose (30 mg/kg), visnagin high dose (60 mg/kg) and visnagin control (60 mg/kg). AP was induced by six injections of cerulein (50 µg/kg, i.p.) on the 7th day and the animals were sacrificed after 6 h of last cerulein dose. Various markers of pancreatic function, oxidative stress and inflammation were assessed. Visnagin was found to be effective in reducing plasma amylase and lipase levels, reduced cerulein induced oxidative stress. Visnagin dose dependently decreased the expression of IL-1ß, IL-6, TNF-α and IL-17. It attenuated the levels of nuclear p65-NFκB. Visnagin improved the antioxidant defence by improving Nrf2 expression and halted pancreatic inflammation by suppressing NFκB and nitrotyrosine expression in the acinar cells. Further, it attenuated the expression of markers of multiple organ dysfunction syndrome and reduced inflammatory cytokines in lungs and intestine. Cumulatively, these findings indicate that visnagin has substantial potential to prevent cerulein induced AP.

Functional nutrition as integrated approach in vitiligo management.

Vitiligo is a common disease of unknown cause that produces disfiguring white patches of depigmentation that can be treated using various new and experimental therapies, such as narrow-band ultraviolet B (NB-UVB) microphototherapy, NB-UVB excimer laser, and monochromatic excimer light. Medical treatments include topical corticosteroids and other topical treatments, such as antioxidants, tacrolimus and pimecrolimus, prostaglandin E, and vitamin D derivatives (Lotti, Berti, & Moretti, 2009). The goal of treating vitiligo is to make it less noticeable either by restoring lost pigment or by eliminating remaining pigment. Functional foods and healthy diet, with nutrients, form a variety of sources, could be considered an integral part, as well as helpful, of vitiligo's medical therapy.

The Medical Treatment of Vitiligo: An Historical Review.

Discolorations of the skin, such as vitiligo, were recognized thousands of years ago. White spots caused by vitiligo and other disorders have caused significant social opprobrium to those disfigured by these pigmentary disorders, throughout history and still in the present day. Treatments have been desperately sought with only partial success. Recent advances suggest that vitiligo and other pigmentary disorders might soon be curable.

Spontaneous stone passage: is it Ammi visnaga effect?

Ammi visnaga was used in Ancient Egypt as an herbal remedy for renal colic. "Khellin", a chemical obtained from Ammi visnaga, was used as a smooth muscle relaxant and has been thought to have pleiotropic effects on urolithiasis. We report a case with multiple ureteral stone passages possibly as a result of medication with an herb preparation, Khellin.

Advanced treatment modalities for vitiligo.

BACKGROUND: Vitiligo is an acquired multifocal and polygenic dyschromia that affects 1% to 3% of the world and presents as multiple depigmented macules and patches. Traditionally, the treatment of vitiligo has focused on pharmacologic interventions, but nearly half of all treated patients fail to respond successfully. OBJECTIVE: Several advanced techniques exist that can aid dermatologists in treating vitiligo in patients who do not respond favorably to traditional pharmacologic treatments. These advanced interventions include the use of the 308-nm excimer laser, total body depigmentation therapy with monobenzyl ether of hydroquinone, microdermabrasion, micropigmentation, khellin-UVA therapy, and surgical management using miniature punch grafting, suction blister grafting, and epidermal cultures. MATERIALS AND METHODS: This article reviews the current literature on these advanced treatment modalities for vitiligo and provides a practical guide for application of these techniques. RESULTS AND CONCLUSION: Our ability to treat vitiligo may be imperfect, but through appropriate patient selection and careful application of one or more of these advanced therapies, successful treatment of vitiligo, even in patients refractory to treatment, can be achieved.

Prevention of renal crystal deposition by an extract of Ammi visnaga L. and its constituents khellin and visnagin in hyperoxaluric rats.

In Egypt, teas prepared from the fruits of Ammi visnaga L. (syn. "Khella") are traditionally used by patients with urolithiasis. The aim of this study was to evaluate whether oral administration of an aqueous extract prepared from the fruits of A. visnaga as well as two major constituents khellin and visnagin could prevent crystal deposition in stone-forming rats. Hyperoxaluria was induced in male Sprague-Dawley rats by giving 0.75% ethylene glycol and 1% ammonium chloride via the drinking water. The Khella extract (KE; 125, 250 or 500 mg/kg) was orally administered for 14 days. The histopathological examination of the kidneys revealed that KE significantly reduced the incidence of calcium oxalate (CaOx) crystal deposition. In addition, KE significantly increased urinary excretion of citrate along with a decrease of oxalate excretion. Comparable to the extract, khellin and visnagin significantly reduced the incidence of CaOx deposition in the kidneys. However, both compounds did not affect urinary citrate or oxalate excretion indicating a mechanism of action that differs from that of the extract. For KE, a reasonably good correlation was observed between the incidence of crystal deposition, the increase in citrate excretion and urine pH suggesting a mechanisms that may interfere with citrate reabsorption. In conclusion, our data suggest that KE and its compounds, khellin and visnagin, may be beneficial in the management of kidney stone disease caused by hyperoxaluria but that it is likely that different mechanism of action are involved in mediating these effects.

Monochromatic excimer light 308 nm in monotherapy and combined with topical khellin 4% in the treatment of vitiligo: a controlled study.

Vitiligo is an acquired depigmentation disorder affecting 1-4% of the world's population. Conventional therapies include steroids, photosensitive topical agents, surgical treatments, and phototherapy. The aim of the study was to evaluate the efficacy of monochromatic excimer light 308 nm (MEL), both as a monotherapy and in combination with khellin 4% ointment in vitiligo. Forty-height patients (36 male and 12 female) affected with vitiligo were enrolled in this open prospective study. Patients were selected and divided into three groups: group I included 16 patients treated with MEL 308 nm once-weekly and oral vitamin E; group II included 16 patients treated with MEL 308 nm once-weekly combined with khellin 4% ointment (MEL-K) and oral vitamin E; group III (control group) included 16 patients treated only with oral vitamin E. Efficacy was assessed at the end of 12 weeks based on the percentage of repigmentation. Group I (MEL-group) showed a moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 10/16 (62.5%), and excellent repigmentation in 4/16 (25%) patients. Group II (MEL-K group) presented moderate repigmentation in 2/16 (12.5%) patients, good repigmentation in 5/16 (31.25%), and excellent repigmentation in 9/16 (56.25%). Group III (control group) showed a moderate repigmentation in 3/16 patients (18.75%), a good repigmentation in 1/16 (6.25%) patient, while 10/16 (62.5%) patients did not show signs of repigmentation. The clinical response achieved in group I and II was higher compared with group III (control group) without showing significant differences. MEL 308 nm, alone and/or combined with khellin 4% offered encouraging results and it may be considered a valid therapeutic option worthy of consideration in the treatment of vitiligo.

Treatment of vitiligo with local khellin and UVA: comparison with systemic PUVA.

Vitiligo is an idiopathic leukoderma often with a progressive course causing destruction of melanocytes. The best methods for achieving cosmetically acceptable re-pigmentation of affected skin appear to be both local and systemic PUVA. They may, however, cause serious side effects, which is an argument for conducting research into new, equally effective photo-chemotherapeutic agents. One of these agents is khellin. We conducted a pilot study in 33 patients to evaluate the effectiveness of local KUVA and systemic PUVA therapy for vitiligo and to compare them in terms of the degree of re-pigmentation, duration of treatment, number of procedures, total UVA dose and side effects. Local KUVA required longer duration of treatment and higher UVA doses. KUVA-induced re-pigmentation depended on the age of the patients (r = -0.61, P = 0.001), and better results were achieved with younger individuals [% re-pigmentation = 81.76 - (1.48 x age in years)]. No side effects were observed in cases of local KUVA treatment. Erythema, itching and gastro-intestinal disturbances occurred with some patients treated with PUVA. The results demonstrate that local KUVA may effectively induce re-pigmentation of vitiligo-affected skin areas to a degree comparable to that achieved when using systemic PUVA, provided that treatment duration is long enough.

From khellin to sodium cromoglycate--a tribute to the work of Dr. R. E. C. Altounyan (1922-1987).

Sodium cromoglycate, which was launched in 1968 by the British company Fisons for the treatment of allergies and asthma, was an absolute novelty in chemical, pharmacological as well as therapeutic respects. The khellin derivative meanwhile did not owe its discovery to the usual strategies for finding drugs. On the contrary, the protective effect of the substance was discovered in a self trial through systematic antigen-induced provocation tests of the medicinal doctor and allergic Roger Ernest Collingwood Altounyan (1922-1987). The only subsequently formed hypothesis of a mast cell stabilising effect of Sodium cromoglcycate did not prove to be valid for the search for similar or more effective substances. A further development of this drug class could not take place because of the lack of suitable pharmacological models.