Clinical Studies Using Topical Melatonin.

Melatonin is ubiquitously present in all animals and plants, where it exerts a variety of physiological activities thanks to its antioxidant properties and its key role as the first messenger of extracellular signaling functions. Most of the clinical studies on melatonin refer to its widespread oral use as a dietary supplement to improve sleep. A far smaller number of articles describe the clinical applications of topical melatonin to treat or prevent skin disorders by exploiting its antioxidant and anti-inflammatory activities. This review focuses on the clinical studies in which melatonin was applied on the skin as a photoprotective, anti-aging, or hair growth-promoting agent. The methodologies and results of such studies are discussed to provide an overall picture of the state of the art in this intriguing field of research. The clinical studies in which melatonin was applied on the skin before exposure to radiation (UV, sunlight, and high-energy beams) were all characterized by an appropriate design (randomized, double-blind, and placebo-controlled) and strongly support its clinical efficacy in preventing or reducing skin damage such as dermatitis, erythema, and sunburn. Most of the studies examined in this review do not provide a clear demonstration of the efficacy of topical melatonin as a skin anti-aging or as a hair growth-promoting agent owing to limitations in their design and/or to the use of melatonin combined with extra active ingredients, except for one trial that suggests a possible beneficial role of melatonin in treating some forms of alopecia in women. Further research efforts are required to reach definitive conclusions concerning the actual benefits of topical melatonin to counteract skin aging and hair loss.

Technological and Physical-Chemical Evaluation of Cotton Gauzes Impregnated with Semisolid Preparations for Wound Healing.

Chronic wounds are marked by an extended healing period during which damaged tissues fail to undergo orderly and timely repair. Examples of chronic wounds encompass venous ulcers, pressure ulcers, and diabetic foot ulcers. The process of wound healing is complex and dynamic, relying on the interplay and response among various cells and mediators. In this study, four marketed wound dressing products based on cotton gauzes impregnated with different semisolid products (namely Betadine® 10%, Connettivina® Bio Plus Fitostimoline® Plus, and Non-Ad® gauzes) have been characterized for their physicochemical properties and ex vivo behaviors. More in detail, the pH and rheological features of semisolid formulations impregnating the gauzes were analyzed along with their ability to adhere to the gauzes. The most promising ones were selected and compared in ex vivo experiments on fresh pig skin. The pH measurements showed an acidic environment for all the tested solutions, albeit with variations in mean values, ranging from 2.66 to 4.50. The outcomes of rheological studies demonstrated that all the semisolid preparations impregnating the gauzes exhibited a pseudoplastic behavior, with significant differences in the pseudoplasticity index across the preparations, which is likely to influence their ability to adhere to the gauze. A rheological study in oscillatory mode revealed rheological behavior typical of a viscous solution only for the cream impregnating non-paraffin gauzes. The other products exhibited rheological behavior typical of a weak gel, which is expected to be advantageous as regards the capability of the semisolid preparation to create and maintain the space within the wound and to provide protection to the injured tissue. Results of ex vivo experiments demonstrated that Fitostimoline® Plus was more effective than Connettivina® Bio Plus in promoting both skin hydration and energy.

NAD-Driven Sirtuin Activation by Cordyceps sinensis Extract: Exploring the Adaptogenic Potential to Promote Skin Longevity.

In recent years, there has been increasing interest in utilizing Traditional Chinese Medicine principles and natural bioactive compounds to combat age-related ailments and enhance longevity. A Cordyceps sinensis mycelium hydroethanolic extract (CsEx), which was standardized in cordycepin and adenosine using UHPLC-DAD, was investigated for its adaptogenic properties using in vitro assays and a double-blind, placebo-controlled clinical trial involving 40 subjects. The CsEx demonstrated activity at a concentration of 0.0006%, significantly increasing sirtuin expression (SirT1: +33%, SirT3: +10%, SirT6: +72%, vs. CTR, p < 0.05) and NAD+ synthesis in HaCat cells (+20% vs. CTR, p < 0.001). Moreover, the CsEx boosted ATP production by 68% in skin cells, correlating with higher skin energy values (+52.0% at D28, p < 0.01) in the clinical trial. Additionally, CsEx notably reduced cytosolic reactive oxygen species (ROS) by 30% in HaCaT cells (p < 0.05) and enhanced collagen production both in vitro (+69% vs. CTR, p < 0.01) and in vivo (+10% vs. D0, p < 0.01), confirmed by ultrasound examination. Furthermore, CsEx's stimulation of fibroblasts, coupled with its antioxidant and energizing properties, led to a significant reduction in wrinkles by 28.0% (D28, p < 0.001). This study underscores Cordyceps sinensis hydroethanolic extract's potential in regulating skin cell energy metabolism and positively influencing the mechanisms associated with skin longevity control.

Annurca Apple Oleolite as Functional Ingredient for the Formulation of Cosmetics with Skin-Antiaging Activity.

The identification of natural remedies for the management of the skin aging process is an increasingly growing issue. In this context, ursolic acid (UA), a ubiquitous molecule, mainly contained in Annurca apple (AA) fruit, has demonstrated valuable cosmetic potential. To this end, in the current study, the AA oleolite (AAO, extract in sunflower oil containing 784.40 ± 7.579 µg/mL of UA) was evaluated to inhibit porcine elastase enzymatic reactions through a validated spectrophotometric method. AAO has shown a valuable capacity to contrast the elastase enzyme with a calculated IC50 of 212.76 mg/mL, in comparison to UA (IC50 of 135.24 µg/mL) pure molecules and quercetin (IC50 of 72.47 µg/mL) which are used as positive controls. In this context and in view of the valuable antioxidant potential of AAO, its topical formulation with 2.5% (w/w) AAO was tested in a placebo-controlled, double-blind, two-arm clinical study on 40 volunteers. Our results indicated that after 28 days of treatment, a significant reduction of the nasolabial fold (-7.2 vs. baseline T0, p < 0.001) and forehead wrinkles (-5.3 vs. baseline T0, p < 0.001) were registered in combination with a valuable improvement of the viscoelastic skin parameters, where skin pliability/firmness (R0) and gross elasticity (R2) were significantly ameliorated (-13% vs. baseline T0, p < 0.001 for R0 and +12% vs. baseline T0, p < 0.001 for R2). Finally, considering the positive correlation between skin elasticity and hydration, the skin moisture was evaluated through the estimation of Trans epidermal water loss (TEWL) and skin conductance.

Into the toxicity potential of an array of parabens by biomimetic liquid chromatography, cell viability assessments and in silico predictions.

Five parabens (PBs) i.e., Methylparaben (MP), Ethylparaben (EP), Isopropylparaben (iPrP), Isobutylparaben (iBuP), Benzylparaben (BzP), and their parent compound i.e., para-hydroxy Benzoic Acid (pHBA), were studied both in vitro and in silico. Specifically, we determined their retention on several both protein- (Human Serum Albumin and α1-acidic glycoprotein) and (phospho) lipid- (immobilized artificial membrane (IAM)) based biomimetic stationary phases to evaluate their penetration potential through the biomembranes and their possible distribution in the body. The IAM phases were based either on phosphatidylcholine (PC) analogues i.e., PC.MG and PC.DD2 or on sphingomyelin (SPH). We also assessed their viability effect on breast cancer cells (MCF-7) via MTT assay subjecting the cells to five different PB concentrations i.e., 100 µM, 10 µM, 1 µM, 0.1 µM and 0.01 µM. Finally, their pharmacokinetics and toxicity were assessed by the ADMET Predictor™ software. Isopropylparaben was found to be more active than 17ß estradiol (E2) employed as positive control, on the screened cell line inducing cell proliferation up to 150 % more of untreated cells. Other analogues showed only a slight/moderate cell proliferation activity, with parabens having longer/branched side chain showing, on average, a higher proliferation rate. Significant linear direct relationships (for PC.DD2 r2 = 0.89, q2 = 0.86, for SPH r2 = 0.89, q2 = 0.85, for both P value < 0.05) were observed between the difference in proliferative effect between the readout and the control at 0.01 µM concentration and the retention on the IAM phases measured at pH 5.0 for all compounds but pHBA, which is the only analyte of the dataset supporting a carboxylic acid moiety. IAM affinity data measured at pH 7.0 were found to be related to the effective human jejunal permeability as predicted by the software ADMET® Predictor, which is relevant when PBs are added to pharmaceutical and food commodities.

Clinical Studies on Topical Curcumin.

BACKGROUND: Curcumin is a polyphenolic compound present in turmeric (Curcuma longa). Curcumin, turmeric powder, and extracts are widely used in traditional Indian medicine and are active ingredients of dietary supplements and cosmeceutical products. The pharmacological properties of curcumin/turmeric as well as the studies performed in vitro, in animal models, and in volunteers have been the objects of a vast literature. Most of the clinical studies report on the effects of curcumin/turmeric administered orally, while only a few describe its topical applications. SUMMARY: This review focuses on clinical studies in which curcumin/turmeric was applied topically to treat various skin conditions based on its antioxidant, anti-inflammatory, and antimicrobial properties. KEY MESSAGES: The clinical studies employing curcumin/turmeric as the only active ingredient allow us to appreciate its therapeutic potential without confounding contributions coming from additional pharmacologically active substances present in the same formulation. Curcumin/turmeric was regarded as an attractive alternative to conventional drugs, such as corticosteroids and antibiotics, thanks to its characteristics of a safe and well-tolerated natural substance.

G-quadruplexes in cancer-related gene promoters: from identification to therapeutic targeting.

INTRODUCTION: Guanine-rich DNA sequences can fold into four-stranded noncanonical secondary structures called G-quadruplexes (G4s) which are widely distributed in functional regions of the human genome, such as telomeres and gene promoter regions. Compelling evidence suggests their involvement in key genome functions such as gene expression and genome stability. Notably, the abundance of G4-forming sequences near transcription start sites suggests their potential involvement in regulating oncogenes. AREAS COVERED: This review provides an overview of current knowledge on G4s in human oncogene promoters. The most representative G4-binding ligands have also been documented. The objective of this work is to present a comprehensive overview of the most promising targets for the development of novel and highly specific anticancer drugs capable of selectively impacting the expression of individual or a limited number of genes. EXPERT OPINION: Modulation of G4 formation by specific ligands has been proposed as a powerful new tool to treat cancer through the control of oncogene expression. Actually, most of G4-binding small molecules seem to simultaneously target a range of gene promoter G4s, potentially influencing several critical driver genes in cancer, thus producing significant therapeutic benefits.

Efficacy of a Multicomponent Nutraceutical Formulation for the Prevention and Treatment of Urinary Tract Stones.

Urolithiasis is a complex and multifactorial disease characterized by the formation of calculi at the urinary tract level. Conventional therapeutic prophylaxis relies on the use of Ca-blockers, alkalis, diuretics, and anti-edema agents, but their prolonged utilization is often limited by several side effects. In this scenario, the aim of the present work was the design of an innovative multi-component nutraceutical formulation (NF) for the management of urinary stones consisting of a synergistic combination of natural aqueous extracts of Oreganum vulgare L. (1% of saponin), Urtica dioica (0.8% of ß-sitosterol), Phyllanthus niruri (15% of tannins w/w), and Ceterach officinarum in association with bromelain, K, and Mg citrate. To assess the potential of NF also in the treatment of uric acid (UA) stones, the effects on the expression of the cellular UA transporters OAT1 and URAT1 were investigated in a renal tubular cell line. In addition, the myorelaxant effect of NF was investigated in a human pulmonary artery smooth muscle cell (HPASMC) model resulting in a decreased muscle contractility of -49.4% (p < 0.01) compared to the control. The treatment with NF also showed a valuable inhibition of in vitro calcium-oxalate crystal formation, both in prevention (-52.3% vs. control, p < 0.01) and treatment (-70.8% vs. control, p < 0.01) experiments. Finally, an ischemic reperfusion rat model was used to evaluate the NF anti-edema effects, resulting in a reduction in the edema-related vascular permeability (Normalized Gray Levels, NGL = 0.40 ± 0.09, p < 0.01, -67.1% vs. untreated rats). In conclusion, the present NF has shown to be a promising natural alternative for managing urinary tract stones.

Dermocosmetic evaluation of a nutricosmetic formulation based on Curcuma.

Endogenous and exogenous factors can alter the skin layer and appearance, determining skin aging. The extracts and isolated molecules from food matrixes can be used to formulate "healthy" antiaging cosmetics. Two different cosmetic approaches can be used to achieve the antiaging effect. It is possible to use topical products based on food extract (cosmeceutical approach) or take a food supplement and apply a topical cosmetic product based on food extract on the surface to be treated (nutricosmetic approach). This work evaluated in vivo the antiaging potential of a nutricosmetic formulation (cream + food supplement) and a cosmeceutical cream based on Curcuma. The choice of the commercial Curcuma extract to be used for experimental purposes was based on the curcuminoid content determined by an HPLC test. Curcuminoids are the bioactive compounds responsible for Curcuma's antioxidant and antiinflammatory properties. Their levels in Curcuma extracts vary according to the storage condition, variety, and pedoclimatic cultivation conditions. The Tewameter® TM300 was used to evaluate the Trans Epidermal Water Loss (TEWL), the Corneometer® CM 825 to determine the moisturizing effect, the Cutometer® to estimate the skin firmness and elasticity, the Dermascan to assess the collagen index, and the Visioface® 1000D to evaluate the wrinkles. The nutricosmetic product showed potential as moisturizing, anti-age, and anti-wrinkle action better than the cosmeceutical product alone.

Gene Expression Programming Model for Tribological Behavior of Novel SiC-ZrO2-Al Hybrid Composites.

In order to improve product format quality and material flexibility, variety of application, and cost-effectiveness, SiC, ZrO2, and Al hybrid composites were manufactured in the research utilizing the powder metallurgy (PM) technique. A model was created to predict the tribological behavior of SiC-ZrO2-Al hybrid composites using statistical data analysis and gene expression programming (GEP) based on artificial intelligence. For the purpose of examining the impact of zirconia concentration, sliding distance, and applied stress on the wear behavior of hybrid composites, a comprehensive factor design of experiments was used. The developed GEP model was sufficiently robust to achieve extremely high accuracy in the prediction of the determine coefficient (R2), the root mean square error (RMSE), and the root relative square error (RRSE). The maximum state of the RMSE was 0.4357 for the GEP-1 (w1) model and the lowest state was 0.7591 for the GEP-4 (w1) model, while the maximum state of the RRSE was 0.4357 for the GEP-1 (w1) model and the minimum state was 0.3115 for the GEP-3 model (w1).

Synthesis of New Zirconium Magnetic Nanocomposite as a Bioactive Agent and Green Catalyst in the Four-Component Synthesis of a Novel Multi-Ring Compound Containing Pyrazole Derivatives.

New nanocomposites containing zirconium were synthesized using microwave irradiation. Their structure was confirmed by vibrating sample magnetometer (VSM) curves, X-ray diffraction (XRD) patterns, scanning electron microscope (SEM) and transmission electron microscopy (TEM) images, Fourier transform infrared spectroscopy (FT-IR), and Brunauer-Emmett-Teller (BET) N2 adsorption/desorption isotherms. After the structure confirmation of the zirconium magnetic nanocomposite, the catalytic properties in the synthesis of pyrazole derivatives were investigated. Next, the biological activities of the zirconium magnetic nanocomposite, such as the antibacterial and antifungal activities, were investigated. The research results showed that the zirconium magnetic nanocomposite has high catalytic properties and can be used as a magnetic nanocatalyst for synthesizing heterocyclic compounds such as pyrazole derivatives in addition to having high biological properties. The unique properties of the nanoparticles can be attributed to their synthesis method and microwave radiation.

Monitoring of Pollutants Content in Bottled and Tap Drinking Water in Italy.

The concentration levels of thirteen organic pollutants and selected heavy metals were investigated in 40 plastics bottled and tap water samples. Some of the selected contaminants have an ascertained or suspected endocrine disrupting activity, such as Bisphenol A (BPA) and its analogs, and Bis 2-ethylhexyl phthalate (DEHP), which are used by industries as plasticizers. The most frequently detected pollutants were Bisphenol AF (BPAF) (detection frequency (DF) = 67.5%, mean 387.21 ng L-1), DEHP (DF = 62.5%, mean 46.19 µg L-1) and BPA (DF = 60.0%, mean 458.57 ng L-1), with higher concentration levels found in tap waters. Furthermore, a possible level of exposure to thirteen pollutants via drinking water intake was calculated. Our findings show that, even though the occurrence of contaminants and heavy metals in drinking waters does not pose an immediate, acute health risk for the population, their levels should be constantly monitored and "hard-wired" into everyday practice. Indeed, the health impact to the continuous and simultaneous intake of a huge variety of xenobiotics from various sources by humans is complex and still not fully understood.

Parabens Permeation through Biological Membranes: A Comparative Study Using Franz Cell Diffusion System and Biomimetic Liquid Chromatography.

Parabens (PBs) are used as preservatives to extend the shelf life of various foodstuffs, and pharmaceutical and cosmetic preparations. In this work, the membrane barrier passage potential of a subset of seven parabens, i.e., methyl-, ethyl-, propyl- isopropyl, butyl, isobutyl, and benzyl paraben, along with their parent compound, p-hydroxy benzoic acid, were studied. Thus, the Franz cell diffusion (FDC) method, biomimetic liquid chromatography (BLC), and in silico prediction were performed to evaluate the soundness of both describing their permeation through the skin. While BLC allowed the achievement of a full scale of affinity for membrane phospholipids of the PBs under research, the permeation of parabens through Franz diffusion cells having a carbon chain > ethyl could not be measured in a fully aqueous medium, i.e., permeation enhancer-free conditions. Our results support that BLC and in silico prediction alone can occasionally be misleading in the permeability potential assessment of these preservatives, emphasizing the need for a multi-technique and integrated experimental approach.

Phenylalanine Butyramide Is a New Cosmetic Ingredient with Soothing and Anti-Reddening Potential.

Human skin is colonized by diverse commensal microbes, making up the skin microbiota (SM), contributing to skin integrity and homeostasis. Many of the beneficial effects aroused by the SM are exerted by microbial metabolites such as short-chain fatty acids (SCFAs), including butyric acid. The SCFAs can be used in cosmetic formulations against skin diseases to protect SM by preserving and/or restoring their natural balance. Unpleasant sensorial properties and unfavorable physico-chemical properties of butyrate strongly limit its cosmetic use. In contrast, some butyrate derivatives, including phenylalanine butyramide (C13H18N2O2, FBA), a solid form of butyric acid, are odorless while retaining the pharmacokinetic properties and safety profile of butyric acid. This study assessed the FBA's permeation across the skin and its soothing and anti-reddening potential to estimate its cosmetic application. The dosage method used to estimate FBA's levels was validated to be sure of analytical results. The FBA diffusion tests were estimated in vitro using a Franz-type vertical diffusion cell. The soothing action was evaluated in vivo by Colorimeter CL400, measuring the erythema index. The results suggest that the FBA represents an innovative way to exploit the benefits of butyric acid in the cosmetic fields since it cannot reach the bloodstream, is odorless, and has a significative soothing action (decrease the erythema index -15.7% after 30', and -17.8% after 60').

An Extract from Ficus carica Cell Cultures Works as an Anti-Stress Ingredient for the Skin.

Psychological stress activates catecholamine production, determines oxidation processes, and alters the lipid barrier functions in the skin. Scientific evidence associated with the detoxifying effect of fruits and vegetables, the growing awareness of the long-term issues related to the use of chemical-filled cosmetics, the aging of the population, and the increase in living standards are the factors responsible for the growth of food-derived ingredients in the cosmetics market. A Ficus carica cell suspension culture extract (FcHEx) was tested in vitro (on keratinocytes cells) and in vivo to evaluate its ability to manage the stress-hormone-induced damage in skin. The FcHEx reduced the epinephrine (-43% and -24% at the concentrations of 0.002% and 0.006%, respectively), interleukin 6 (-38% and -36% at the concentrations of 0.002% and 0.006%, respectively), lipid peroxide (-25%), and protein carbonylation (-50%) productions; FcHEx also induced ceramide synthesis (+150%) and ameliorated the lipid barrier performance. The in vivo experiments confirmed the in vitro test results. Transepidermal water loss (TEWL; -12.2%), sebum flow (-46.6% after two weeks and -73.8% after four weeks; on the forehead -56.4% after two weeks and -80.1% after four weeks), and skin lightness (+1.9% after two weeks and +2.7% after four weeks) defined the extract's effects on the skin barrier. The extract of the Ficus carica cell suspension cultures reduced the transepidermal water loss, the sebum production, the desquamation, and facial skin turning to a pale color from acute stress, suggesting its role as an ingredient to fight the signs of psychological stress in the skin.

The occurrence of selected endocrine-disrupting chemicals in water and sediments from an urban lagoon in Southern Italy.

Endocrine-disrupting chemicals (EDCs) are agents able to exert perturbation toward the endocrine system via a broad array of signalling pathways. Some EDCs are released into the environment as a result of antropogenic activities. Analytical surveillance plays a critical role in investigating the prevalence of such chemicals in environmental samples. A study was carried out in a lagoon in Southern Italy, a water basin relates to the sea through a mouth channel, making this water body a "dynamic environment". The screening of fourteen EDCs in surface waters and sediments, includes a fast and cost-effective sample preparation, based on a solid-liquid (sediments) and liquid-liquid (surface waters) extraction and a chromatographic analysis by liquid chromatography tandem UV and fluorescence detection. Only four chemicals out the fourteen investigated EDCs were detected in both matrices with a frequency higher than 60%. The average concentrations of the single EDC were higher in sediments (730-155.000 ng kg-1  dw) than in surface waters (132-28.000 ng L-1 ). Limited to the assayed EDCs, the ecosystem has a low risk regarding to the conservation of biodiversity of the animal species living thereby, since the total estrogenic activity does not exceed 1 ng L-1 . PRACTITIONER POINTS: Occurrence of selected EDCs was investigated in an Italian lagoon in Southern Italy. BPAF, BADGE, and BPA were the most frequently and highly detected compounds in both waters and sediments. Concentration levels were greater in the sediment than in water samples. Low risk for the ecosystem biodiversity concerning investigated EDCs.

Plant cell culture extract of Cirsium eriophorum with skin pore refiner activity by modulating sebum production and inflammatory response.

Facial pore enlargement is considered a significant esthetic and health concern in skincare cosmetics. The pores fulfill the critical function of keeping the skin surface hydrated and protected against microbial infections. The hyperseborrhea, the stress factors, and the hormonal triggers can cause pore size enlargement, causing higher susceptibility of the skin to microbe aggressions and inflammatory reactions. Thus, reducing excessive sebum production and keeping functional pores are two of the most requested activities in skincare cosmetics. A Cirsium eriophorum cell culture extract was investigated for its role in sebum regulation, stratum corneum desquamation, and anti-inflammation. The extract was able to regulate essential markers associated with sebum secretion and pore enlargements, such as the enzyme 5α-reductase, which plays a central role in sebum production, and the trypsin-like serine protease Kallikrein 5, which promotes skin exfoliation and antimicrobial response. Moreover, the extract showed a sebum-normalizing and pore refining activity in individuals having seborrheic or acne-prone skins, suggesting a role of the C. eriophorum extract in rebalancing altered skin conditions responsible for pore enlargement.

Validation of Rapid Enzymatic Quantification of Acetic Acid in Vinegar on Automated Spectrophotometric System.

Vinegar is produced from the fermentation of agricultural materials and diluted acetic acid (diluted with water to 4-30% by volume) via sequential ethanol and acetic acid fermentation. The concentration of acetic acid must be measured during vinegar production. A Community method for analyzing acetic acid in vinegar is a non-specific method based on the assumption that the total acid concentration of the vinegar is attributable to the acetic acid. It consists of titration with a strong base in the presence of an indicator. This test is laborious and has a time-consuming character. In this work, a highly specific automated enzymatic method was validated, for the first time, to quantify the acetic acid in the wine vinegar, in terms of linearity, precision, repeatability, and uncertainty measurement. The results were compared to the Community method of analysis. Regression coefficient ≅ 1 and the normal distribution of residuals in the ANOVA test confirmed the method's linearity. LLOD (0.946 ppm) and LLOQ (2.00 ppm) defined the method's sensitivity. The results of the tested and the Community methods, linearly distributed in the Shapiro-Wilk test, confirmed the method's repeatability. The few anomalous data in the Huber test were due to random errors. The high selectivity of the enzymatic method, which exclusively measures acetic acid concentration, determined the significant differences between the two tests, examined in the accuracy determination. The enzymatic method can be considered applicable since its precision and uncertainty were lower than the Community method values (relative percentage deviations = 10%). The enzymatic method compared to the Community method reduces the analysis time and the risk of errors due to operators (avoid pipetting errors and wrong calculations), minimizes solvent and the sample consumption and guarantees assay quality through method standardization.

Pharmacological and molecular docking assessment of cryptotanshinone as natural-derived analgesic compound.

Medicinal plants from traditional chinese medicine are used increasingly worldwide for their benefits to health and quality of life for the relevant clinical symptoms related to pain. Among them, Salvia miltiorrhiza Bunge is traditionally used in asian countries as antioxidant, anticancer, anti-inflammatory and analgesic agent. In this context, several evidences support the hypothesis that some tanshinones, in particular cryptotanshinone (CRY), extracted from the roots (Danshen) of this plant exhibit analgesic actions. However, it is surprisingly noted that no pharmacological studies have been carried out to explore the possible analgesic action of this compound in terms of modulation of peripheral and/or central pain. Therefore, in the present study, by using peripheral and central pain models of nociception, such as tail flick and hot plate test, the analgesic effect of CRY in mice was evaluated. Successively, by the aim of a computational approach, we have evaluated the interaction mode of this diterpenoid on opioid and cannabinoid system. Finally, CRY was dosed in mice serum by an HPLC method validated according to European Medicines Agency guidelines validation rules. Here, we report that CRY displayed anti-nociceptive activity on both hot plate and tail flick test, with a prominent long-lasting peripheral analgesic effect. These evidences were indirectly confirmed after the daily administration of the tanshinone for 7 and 14 days. In addition, the analgesic effect of CRY was reverted by naloxone and cannabinoid antagonists and amplified by arginine administration. These findings were finally supported by HPLC and docking studies, that revealed a noteworthy presence of CRY on mice serum 1 h after its intraperitoneal administration and a possible interaction of tested compound on µ and k receptors. Taken together, these results provide a new line of evidences showing that CRY can produce analgesia against various phenotypes of nociception with a mechanism that seems to be related to an agonistic activity on opioid system.