Molecular Analysis of the Melanogenesis Inhibitory Effect of Saponins-Rich Fraction of Argania spinosa Leaves Extract.

Plant saponins are abundant and diverse natural products with a great potential for use in drug-discovery research. Here, we evaluated extracts of saponins-rich fractions of argan leaves and argan oil extraction byproducts (shell, pulp, press cake) for their effect on melanogenesis. Results show that from among the samples tested, only the saponins-rich fraction from leaves (ALS) inhibited melanin production in B16 murine melanoma (B16) cells. The mechanism of the melanogenesis inhibition was elucidated by determining the protein and mRNA expression of melanogenesis-associated enzymes tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT), and microphthalmia-associated transcription factor (MITF), and performing DNA microarray analysis. Results showed that 10 µg/mL ALS significantly inhibited melanogenesis in B16 cells and human epidermal melanocytes by 59% and 48%, respectively, without cytotoxicity. The effect of ALS on melanogenesis can be attributed to the decrease in TYR, TRP1, and MITF expression at the protein and mRNA levels. MITF inhibition naturally led to the downregulation of the expression of Tyr and Trp1 genes. Results of the DNA microarray analysis revealed the effect on melanogenesis-associated cAMP and Wnt signaling pathways' genes. The results of this study suggest that ALS may be used in cosmeceuticals preparations for hyperpigmentation treatment.

Safety Assessment and Pain Relief Properties of Saffron from Taliouine Region (Morocco).

Saffron is the most expensive spice in the world. In addition to its culinary utilization, this spice is used for medicinal purposes such as in pain management. In this study, the analgesic activity of Crocus sativus stigma extract (CSSE) was evaluated in rodents and its possible physiological mechanism was elucidated. The anti-nociceptive effect of CSSE was evaluated using three animal models (hot plate, writhing, and formalin tests). The analgesic pathways involved were assessed using various analgesia-mediating receptors antagonists. The oral administration of CSSE, up to 2000 mg/kg, caused no death or changes in the behavior or in the hematological and biochemical blood parameters of treated animals nor in the histological architecture of the animals' livers and kidneys. CSSE showed a central, dose-dependent, anti-nociceptive effect in response to thermal stimuli; and a peripheral analgesic effect in the test of contortions induced by acetic acid. The dual (central and peripheral) analgesic effect was confirmed by the formalin test. The anti-nociceptive activity of CSSE was totally or partially reversed by the co-administration of receptor antagonists, naloxone, atropine, haloperidol, yohimbine, and glibenclamide. CSSE influenced signal processing, by the modulation of the opioidergic, adrenergic, and muscarinic systems at the peripheral and central levels; and by regulation of the dopaminergic system and control of the opening of the ATP-sensitive K+ channels at the spinal level. The obtained data point to a multimodal mechanism of action for CSSE: An anti-inflammatory effect and a modulation, through different physiological pathways, of the electrical signal generated by the nociceptors. Further clinical trials are required to endorse the potential utilization of Moroccan saffron as a natural painkiller.

Flaxseed extract reduces tissue accumulation and enhances urinary excretion of chondroitin sulphate in the rat: a possible new path in substrate reduction therapy for mucopolysaccharidosis.

CONTEXT: Chondroitin 6 sulphate (C6S) is a glycosaminoglycan (GAG) whose accumulation is notable in mucopolysaccharidosis type IVA and VII. Flaxseed, Linum usitatissimum L. (Linaceae) (FS), is reported to have comparable properties to those of soybean, a source of genistein, a potential new treatment for MPSs. OBJECTIVE: We assess the effect of total ethanol flaxseed extract (EFSE) in an animal model of C6S accumulation. MATERIALS AND METHODS: The study was performed in adult male Wistar rats (n = 24) for 15 successive days. The animals were divided into four groups: (1) control injected with physiological saline buffer, (2) intoxicated rats injected intraperitoneally with C6S, (3) intoxicated with C6S and treated with EFSE, and (4) treated with EFSE. All groups were subjected to histopathological and biochemical studies. The antioxidant and phytochemical properties of EFSE were examined. RESULTS: Dry EFSE contains total phenols (6.28 mg EAG/g), condensed tannins (2.98 mg ECAT/g) and flavonoids (0.44 mg ECAT/g) with high antioxidant potential [RPE (IC50 = 8.37 ± 0.176), DPPH (IC50 = 12.79 ± 0.273)]. The LD50 is higher than 5000 mg/kg. The histopathological examination showed an accumulation of C6S in the C6S intoxicated group, which disappeared in the C6S-EFSE treated group. GAGs assays showed an increased excretion in the C6S intoxicated group and increased excretion of 14% in the C6S-EFSE group compared to the C6S group. DISCUSSION AND CONCLUSIONS: EFSE showed significant potential for chelation. Its use for the treatment of GAG accumulation could be suggested and generalized to a larger study population.

Anti-Inflammatory, Antioxidant, Chemical Characterization, and Safety Assessment of Argania spinosa Fruit Shell Extract from South-Western Morocco.

Argania spinosa (L.) plays an important role in the Moroccan agroeconomy, providing both employment and export revenue. Argan oil production generates different by-products with functionalities that are not yet investigated, in particular, the shell fruit. The present study aims, for the first time, at evaluating the acute and subacute toxicity, anti-inflammatory, and antioxidant effects of argan fruit shell ethanol extract (AFSEE). The LD50 of AFSEE was determined to be greater than the 5000 mg/kg body weight of mice. No significant variation in the body and organ weights was observed after 28 days of AFSEE treatment compared to that of the control group. Biochemical parameters and histopathological examination revealed no toxic effects of AFSEE. The AFSEE produced a significant inhibition of xylene-induced ear edema in mice. AFSEE reduced significantly the paw edema in mice after carrageenan injection. The chemical characterization showed that AFSEE contains a high level of total phenol content, flavonoids, condensed tannins, and flavanols. The obtained IC50 of DPPH, ABTS, reducing power, and ß-carotene demonstrates that AFSEE has a potential antioxidant effect. The results indicate that AFSEE was safe and nontoxic to mice even at higher doses. Furthermore, the present findings demonstrate that AFSEE has potential anti-inflammatory and antioxidant activities.

Argania Spinosa Fruit Shell Extract-Induced Melanogenesis via cAMP Signaling Pathway Activation.

We have previously reported that argan oil and argan press-cake from the kernels of Argania spinosa have an anti-melanogenesis effect. Here, the effect of argan fruit shell ethanol extract (AFSEE) on melanogenesis in B16F10 cells was determined, and the mechanism underlying its effect was elucidated. The proliferation of AFSEE-treated B16F10 cells was evaluated using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, while the melanin content was quantified using a spectrophotometric method. The expression of melanogenesis-related proteins was determined by Western blot and real-time PCR, while global gene expression was determined using a DNA microarray. In vitro analysis results showed that the melanin content of B16F10 cells was significantly increased by AFSEE, without cytotoxicity, by increasing the melanogenic enzyme tyrosinase (TRY), tyrosinase related-protein 1 (TRP1), and dopachrome tautomerase (DCT) protein and mRNA expression, as well as upregulating microphthalmia-associated transcription factor (MITF) expression through mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) and p38, and the cyclic adenosine monophosphate (cAMP) signaling pathway, as indicated by the microarray analysis results. AFSEE's melanogenesis promotion effect is primarily attributed to its polyphenolic components. In conclusion, AFSEE promotes melanogenesis in B16F10 cells by upregulating the expression of the melanogenic enzymes through the cAMP-MITF signaling pathway.AFSEE may be used as a cosmetics product component to promote melanogenesis, or as a therapeutic against hypopigmentation disorders.

Crocus sativus restores dopaminergic and noradrenergic damages induced by lead in Meriones shawi: A possible link with Parkinson's disease.

Lead (Pb) is a metal element released into the atmosphere and a major source of environmental contamination. The accumulation and concentration of this metal in a food web may lead to the intoxication of the body, more precisely, the nervous system (NS). In addition, Pb-exposure can cause structural and functional disruption of the NS. Studies have shown that Pb-exposure could be a risk factor in the development of Parkinson's disease (PD). The latter is related to dopaminergic deficiency that may be triggered by genetic and environmental factors such as Pb intoxication. In this study, we have evaluated, in one hand, the neurotoxic effect of Pb (25 mg / kg B.W i.p) for three consecutive days on dopaminergic system and locomotor performance in Merione shawi. In the other hand, the possible restorative potential of C. sativus (CS) (50 mg / kg BW) by oral gavage. The immunohistochemical approach has revealed that Pb-intoxicated Meriones show a significant increase of Tyrosine Hydroxylase (TH) levels within the Substantia Nigra compacta (SNc), Ventral Tegmental Area (VTA), Locus Coeruleus (LC), Dorsal Striatum (DS) and Medial Forebrain Bundle (MFB), unlike the control meriones, a group intoxicated and treated with Crocus sativus hydroethanolic extract (CSHEE) and treated group by CSHEE. Treatment with CSHEE, has shown a real potential to prevent all Pb-induced damages. In fact, restores the TH levels by 92%, 90%, 88%, 90% and 93% in SNc, VTA, LC, DS and MFB respectively, similarly, locomotor activity dysfunction in Pb-intoxicaed meriones was reinstated by 90%. In this study, we have revealed a new pharmacological potential of Crocus sativus that can be used as a neuroprotective product for neurodegenerative disorders, especially, which implying dopaminergic and noradrenergic injuries, like PD, trigged by heavy metals.