Efficacy and Tolerability of a Scutellaria lateriflora L. and Cistus × incanus L.-Based Chewing Gum on the Symptoms of Gingivitis: A Monocentric, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Preclinical studies have shown that the combination of Cistus × incanus L. and Scutellaria lateriflora L. extracts exerts beneficial effects on oral health against gingivitis. Thus, this study aimed to assess the tolerability of a chewing gum and its efficacy on gingivitis in a double-blind, placebo-controlled clinical trial. Enrolled subjects (n = 60, 18-70 years) were randomized to receive two chewing gums or a placebo daily for 3 months. At baseline (t0) and monthly (t1, t2, and t3) timepoints, the Quantitative Gingival Bleeding Index (QGBI), the Modified Gingival Index (MGI), and the Oral Health 15 items (OH-15)] were employed to assess potential improvements in gingivitis. Pain was self-quantified via the Visual Analogue Scale (VAS), and the Clinical Global Impression Scale for Severity of illness (CGI-S) helped in evaluating the oral general conditions. This study is listed on the ISRCTN registry. At t3, the QGBI, MGI, OH-15, VAS, and CGI-S values decreased in the treated but not in the placebo group (ß = 0.6 ± 0.1, t176 = 3.680, p < 0.001; ß = 0.87 ± 0.21, t115 = 4.263, p < 0.001; ß = 5.3 ± 2.5, t172 = 2.086, p = 0.038; ß = 3.16 ± 0.51, t88 = 6.253, p < 0.001; and ß = 1.09 ± 0.32, t83 = 3.419, p < 0.001, respectively). A significant improvement in gingival health occurred after a 3-month intervention with the chewing gums containing S. lateriflora and C. incanus extracts.

Chemical composition and potential antioxidant, anti-inflammatory, and analgesic efficacy of Cistus albidus L.

This study aims to assess the chemical composition of the aqueous extract of Cistus albidus L. leaves, as well as the potential of aqueous and hydroethanol extracts of the leaves and seeds as analgesic, anti--inflammatory, and antioxidant agents. The contents of phenolics and inorganic constituents were determined in C. albidus seeds and leaves; antioxidant capacity was assessed by 3 complementary and diverse tests. The carrageenan-induced paw edema technique was used to investigate the anti-inflammatory effect in vivo, and albumin denaturation to evaluate the anti-inflammatory effect in vitro. The acetic acid-induced contortion test, the tail-flick test, and the plantar test were used to assess the analgesic effi cacy in vivo. Chemical analysis was performed by UPLC-MS/MS to quantify several phenolic compounds including catechin (1,627.6 mg kg-1), quercitrin (1,235.8 mg kg-1) and gallic acid (628. 2 mg kg-1). The ICP analysis revealed that potassium and calcium were the main inorganic components in the seeds and leaves of C. albidus. The hydroethanolic extract of the leaves showed the highest content of polyphenols/flavonoids, whereas the highest value of proantho cyanidins was detected in the aqueous extract of the seeds. All extracts showed potent antioxidant activity related to different phenolic compounds (quercetin, gallic acid, astragalin, catechin, and rutin). The aqueous extract of the leaves strongly inhibited paw edema (76.1 %) after 6 h of treatment and showed maximal inhibition of protein denaturation (191.0 µg mL-1 for 50 % inhibition) and analgesic activity in different nociceptive models. The presented data reveal that C. albidus extracts potentially show antioxidant, anti-inflammatory, and analgesic activities that could confirm the traditional use of this plant.

Ionomic analysis, polyphenols characterization, analgesic, antiinflammatory and antioxidant capacities of Cistus laurifolius leaves: in vitro, in vivo, and in silico investigations.

This study aims to investigate the chemical and mineral composition, antioxidant, analgesic, and anti-inflammatory effects of the aqueous extract of Cistus laurifolius var. atlanticus Pit. (Cistaceae). Additionally, molecular docking interactions of various ligands with antioxidant protein target urate oxidase (1R4U) and anti-inflammatory protein target cyclooxygenase-2 (3LN1), revealing potential dual activities and highlighting specific residue interactions. The chemical characterization focused at first glance on the mineral composition which showed that C. laurifolius extract is a mineral-rich source of potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), phosphorus (P), and zinc (Zn). We next performed, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, the latter showed various polyphenols in C. laurifolius extract including Gallic acid as the predominant polyphenol. Isoquercetin, Taxifolin and Astragalin were also among the major flavonoids detected. The antioxidant capacity of C. laurifolius leaves was tested using 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1- picrylhydrazyl (DPPH) and reducing power (RP) assays. In vitro analysis of the anti-inflammatory property of C. laurifolius leaves was conducted by the albumin denaturation test and the in vivo was assessed in the sequel by carrageenan-induced paw edema test. The analgesic activity was evaluated in vivo using tail flick, acetic acid-induced contortion, and plantar tests. The findings showed that the leave extract had a powerful antioxidant activity with an IC50 values of 2.92 ± 0.03 µg/mL (DPPH) and 2.59 ± 0.09 µg/mL (in RP test). The studied extract strongly abolished the induced inflammation (82%). Albumin denaturation test recorded an IC50 value of 210 µg/mL. Importantly, the oral administration of C. laurifolius extract considerably reduced the nociceptive effect of acetic acid in rats, showing a significant analgesic effect in a dose-related manner. Altogether, our results showed that C. laurifolius can be a promising source of phytochemicals for drug development potential.

Study of the Analgesic Potential of the Ethanolic Extract of Moroccan Cistus ladanifer L.

AIMS: The study aimed to analyze the analgesic activity of Cistus ladanifer L. BACKGROUND: Cistus ladanifer L. is a fragrant shrub of the Cistaceae family widespread in the Mediterranean basin, it has various biological activities, including antidiabetic and antihypertensive effects. OBJECTIVES: The objective of this work was to study the phytochemical profile, the acute toxicity and the analgesic power of the ethanolic extract of the species Cistus ladanifer L. (C. ladanifer) collected in Northern Morocco. METHODS: The evaluation of antinociceptive activity in mice was performed using two validated models, the formalin-induced paw-licking model and the acetic acid-provoked writhing test. RESULTS: According to the results, five phenolic compounds were identified in the ethanolic extract by HPLC-MS/MS. As regards the acute toxicity study, the results showed no mortality or clinical symptoms in mice treated to compare the control group at doses up to 5,000 mg/kg BW. Regarding the analgesic effect, the ethanolic extract at the doses of 400 and 800 mg/kg, BW showed a statistically significant (p <0.05) and dose-dependent analgesic effect in two nociceptive tests. On the other hand, in the syrup of ethanolic extract at the dose of 800 mg/kg, BW expressed the most superior pain-inhibiting effect in both tests, producing an analgesic effect equivalent to that of the reference drug (indomethacin). CONCLUSION: These findings provide pharmacological justification that might aid in the development of a natural anti-nociceptive medication as an alternative to chemical analgesic drugs.

Efficacy of Two Moroccan Cistus Species Extracts against Acne Vulgaris: Phytochemical Profile, Antioxidant, Anti-Inflammatory and Antimicrobial Activities.

BACKGROUND: The genus Cistus L. (Cistaceae) includes several medicinal plants growing wild in the Moroccan area. Acne vulgaris (AV) is a chronic skin disorder treated with topical and systemic therapies that often lead to several side effects in addition to the development of antimicrobial resistance. Our study aimed to investigate the bioactivity of extracts of two Moroccan Cistus species, Cistus laurifolius L. and Cistus salviifolius L., in view of their use as potential coadjuvants in the treatment of mild acne vulgaris. METHODS: Targeted phytochemical profiles obtained by HPLC-DAD and HPLC-ESI/MS analyses and biological activities ascertained by several antioxidants in vitro chemical and cell-based assays of the leaf extracts. Moreover, antimicrobial activity against Gram-positive and Gram-negative bacteria, and Candida albicans was evaluated. RESULTS: Analyses revealed the presence of several polyphenols in the studied extracts, mainly flavonoids and tannins. Cistus laurifolius L. and Cistus salviifolius L. possessed good biological properties and all extracts showed antibacterial activity, particularly against Staphylococcus aureus, S. epidermidis, and Propionibacterium acnes, identified as the main acne-causing bacteria. CONCLUSION: The results suggest that examined extracts are promising agents worthy of further studies to develop coadjuvants/natural remedies for mild acne treatment.

Comparative Evaluation of Polyphenol Contents and Biological Activities of Five Cistus L. Species Native to Turkey.

In this study phytochemical compounds and antioxidant capacity, cytotoxic, antimicrobial and anti-biofilm activities of hydroethanolic extracts of five Cistus species (C. creticus L., C. laurifolius L., C. monspeliensis L., C. parviflorus Lam. and C. salviifolius L.) distributed in Turkey were investigated. (+)-catechin, epigallocatechin gallate, quercetin-3-O-rutinoside, quercetin-3-O-glucoside, kaempferol-3-O-glucoside, luteolin were detected in different amounts. Strongest antioxidant capacities were observed with C. creticus, and C. parvifolius (0.476 and 0.452, respectively). Minimum inhibitory concentrations (MIC) of the extracts were determined between 32 and 128 µg/mL against different bacteria and Candida strains. C. monspeliensis and C. laurifolius extracts were inhibited the biofilm production levels of three Gram-negative bacteria (E. coli, S. enterica, P. aeruginosa), two Gram-positive bacteria (S. aureus, B. subtilis) and three Candida strains (C. albicans, C. parapsilosis, C. krusei). C. creticus extract showed strongest cytotoxic activity against human breast adenocarcinoma (MCF-7) and prostate cell lines (PC-3) (IC50 : 14.04±2.78 µg/mL and 34.04±2.74 µg/mL, respectively) among all plants tested.

Thymus mastichina (L.) L. and Cistus ladanifer L. for skin application: chemical characterization and in vitro bioactivity assessment.

ETHNOPHARMACOLOGICAL RELEVANCE: Thymus mastichina (L.) L. (TM) and Cistus ladanifer L. (CL) are two Portuguese autochthonous species with traditional skin application in folk medicine. TM is majorly known for its antiseptic and wound healing properties, as an external anti-inflammatory agent and for its application in folk cosmetics and hygiene products. Its use in acne vulgaris has also been reported. CL is traditionally used in remedies for wounds, ulcers and other skin ailments such as psoriasis and eczema. Its application has been found useful due to its anti-inflammatory, astringent, wound healing and antiseptic properties. AIM OF THE STUDY: With this work, we aimed to investigate relevant bioactivities related with the traditional application of TM and CL essential oils (EOs) and hydrolates (by-products of EO production) in skin ailments. Specifically their in vitro antioxidant, anti-inflammatory, cytotoxic, wound healing and antimicrobial properties were evaluated. The chemical composition of both EOs and respective hydrolates was also characterized. MATERIALS AND METHODS: Chemical characterization of EOs and hydrolates was performed by GC-FID and GC-MS. Cellular biocompatibility was evaluated using the MTT assay in macrophages (RAW 264.7) and fibroblasts (L929) cell lines. Anti-inflammatory activity was investigated by studying nitric oxide (NO) production by macrophages with Griess reagent. Wound healing potential was evaluated with the scratch-wound assay. The antioxidant potential was studied by the DPPH scavenging method. Antimicrobial activity was evaluated by broth microdilution assay against relevant microbial strains and skin pathogens, namely Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Aspergillus brasiliensis. RESULTS: The major compounds present in TM and CL EOs were 1,8-cineole and α-pinene, respectively. 1,8-cineole and E-pinocarveol were the major compounds in the correspondent hydrolates. CL EO presented the highest anti-inflammatory potential [EC50 = 0.002% (v/v)], still with significant cytotoxicity [IC50 = 0.012% (v/v)]. TM preparations presented anti-inflammatory potential, also presenting higher biocompatibility. The same profile was present on fibroblasts regarding biocompatibility of the tested preparations. CL EO and hydrolate increased fibroblasts' migration by 155.7% and 148.4%, respectively. TM hydrolate presented a milder activity than CL hydrolate, but wound healing potential was still present, increasing cell migration by 125.1%. All preparations presented poor antioxidant capacity. CL EO presented higher antimicrobial activity, with MICs ranging from 0.06% (v/v) to 2% (v/v), against different microorganisms. CONCLUSIONS: Anti-inflammatory and skin repairing potential were present for CL preparations. TM hydrolate presented an interesting biocompatible profile on both cell lines, also presenting anti-inflammatory potential. Furthermore, EOs from both species presented antimicrobial activity against a panel of different microorganisms. These in vitro bioactivities support some of their traditional skin applications, specifically regarding their antiseptic, wound healing and anti-inflammatory uses.

Phytochemistry and Antihyperglycemic Potential of Cistus salviifolius L., Cistaceae.

Cistus salviifolius has been previously reported as a traditional remedy for hyperglycemia. However, the plant has been scarcely investigated from scientific point of view. Thus, the aim was to examine the chemical composition and to evaluate its antioxidant and antihyperglycemic potential in vitro. Aqueous and ethanolic extracts were evaluated for total phenolic, tannin, and flavonoid content using spectrophotometric methods. Detailed chemical characterization was performed by high-performance liquid chromatography (HPLC-DAD). The volatile organic compounds (VOCs) profile was assessed by gas chromatography technique. The potential in diabetes treatment was evaluated through tests of free radicals neutralization, inhibition of lipid peroxidation process, and test of ferric ion reduction; activity in tests of inhibition of α-amylase, α-glucosidase and dipeptidyl peptidase-4 was also evaluated. High content of phenolics (majority being tannins) was detected; detailed HPLC analysis revealed high content of gallic acid, followed by rutin, chlorogenic and caffeic acids. The VOCs analysis determined sesquiterpene hydrocarbons and oxygenated sesquiterpenes as the main groups of compounds. The assays classified extracts as potent neutralizers of 2,2-diphenyl-1-picrylhydrazil and nitroso radicals formation and potent inhibitors of α-amylase and α-glucosidase. In conclusion, Cistus salviifolius represents a rich source of phenolics and essential oil with sesquiterpenes. The established results suggested its promising antioxidant and antihyperglycemic activities.

Phytochemical profile, in vivo anti-inflammatory and wound healing activities of the aqueous extract from aerial parts of Cistus ladanifer L.

Cistus ladanifer L. is a Mediterranean shrub, well recognized for its many pharmacological properties. The present study aimed to investigate the phytochemical profile, the in vivo anti-inflammatory and the wound healing activities of the aqueous extract from its aerial parts (AECL). The in vivo anti-inflammatory and the wound healing properties were evaluated by carrageenan-induced paw edema (CAECL) and burn wound in rats, respectively. The results showed that six compounds belonging to flavonoids and tannins were identified in the AECL extract. Moreover, the AECL administrated orally at a dose of 500 mg/kg significantly reduced edema with a percentage of 72 % in terms of inflammation inhibition, using indomethacin as reference drug. On the other hand, when administrated topically, both doses of CAECL cream (5 % and 10 %) manifested a significant anti-inflammatory action using diclofenac as reference drug with a percentage reduction of inflammation that reached 85 % (CAECL-10). As far as wound healing is concerned, the CAECL showed higher effect at a dose of 10 % (CAECL-10) producing a wound contraction of 96 %, similar to that of the reference drug. The findings of the present study indicate that the aqueous extract from aerial parts of Cistus ladanifer L. display strongly anti-inflammatory and wound healing effects to be advantageously used for medical purposes.

Antioxidant and Antiglycation Effects of Cistus × incanus Water Infusion, Its Phenolic Components, and Respective Metabolites.

Reactive oxygen and carbonyl species promote oxidative and carbonyl stress, and the development of diabetes, metabolic syndrome, cardiovascular diseases, and others. The traditional herb Cistus × incanus is known for its antioxidant properties; therefore, the current study aimed to assess how the chemical composition of a C. incanus water infusion corresponds with its antioxidative and antiglycative effects in vitro. The composition of infusions prepared from commercial products was analyzed with UHPLC-ESI-qTOF-MS. Total phenolics, flavonoids, and non-flavonoid polyphenols were determined. Antioxidant activity of infusions and selected polyphenols was investigated using DPPH, ABTS, and FRAP. Fluorometric measurements and methylglyoxal capture were performed to investigate the antiglycation activity. PCA and PLS-DA models were applied to explore the correlation between chemical and antioxidant results. The principal flavonoids in C. incanus were flavonols. In vitro tests revealed that a stronger antioxidant effect was demonstrated by plant material from Turkey rich in flavonoids, followed by Albania and Greece. Flavonols and ellagic acid displayed stronger antiradical and reducing power than EA-derived urolithins. Hyperoside was the most potent inhibitor of glycation. The results indicate that flavonoids are primarily responsible for rock rose antioxidant and antiglycation properties. PLS-DA modeling can be used to identify the origin of plant material with sensitivity and specificity exceeding 86%.

Essential Oils Derived from Cistus Species Activate Mitochondria by Inducing SIRT1 Expression in Human Keratinocytes, Leading to Senescence Inhibition.

Cistus L. is a genus of dicotyledonous perennial herbaceous plants. Cistus species have been commonly used in folk medicine in the Mediterranean region. In the present study, the biological activities of essential oils derived from Cistus species (Cistus laurifolius, C. monspeliensis, C. creticus, and C. salviifolius) were evaluated. Essential oils derived from C. laurifolius and C. monspeliensis were found to augment the expression of SIRT1, an anti-aging gene, in the normal culture of HaCaT cells. Furthermore, these essential oils increased the number and size of mitochondria and augmented their activity. These effects were thought to be caused by the up- and downregulated expression of MITOL and Drp1 in HaCaT cells, respectively, in response to the essential oil treatment. In addition, these essential oils were found to attenuate ultraviolet-B-induced mitochondrial damage and cellular senescence in HaCaT cells. These findings indicate that essential oils derived from C. laurifolius and C. monspeliensis may inhibit skin aging through mitochondrial regulation via SIRT1 activation.

The use of Dalmatian pyrethrum daisy and an excipient in the treatment of seborrheic dermatitis.

The active ingredients of the Pyretrin-D trichological cosmetic series, namely benzyl benzoate, Dalmatian pyrethrum daisy, Cistus incanus, tea tree oil and geranium oil, almond acid and arginine were tested in respect to the treatment of seborrheic dermatitis. The paper describes the application of Dalmatian pyrethrum daisy and the excipient. Methods and devices used to confirm the effectiveness of the tested formulations included the TrichoScope Polarizer Dino-Lite (MEDL4HM) and the scanning electron microscope (SEM).

Influence of In Vitro Human Digestion Simulation on the Phenolics Contents and Biological Activities of the Aqueous Extracts from Turkish Cistus Species.

Oxidative stress is one of the significant precursors of various metabolic diseases such as diabetes, Parkinson's disease, cardiovascular diseases, cancer, etc. Various scientific reports have indicated that secondary plant metabolites play an important role in preventing oxidative stress and its harmful effects. In this respect, this study was planned to investigate the phenolic profile and antioxidant and antidiabetic potentials of the aqueous extracts from Turkish Cistus species by employing in vitro methods. In vitro digestion simulation procedure was applied to all extracts to estimate the bioavailability of their phenolic contents. Total phenolic, flavonoid, phenolic acid and proanthocyanidin contents were determined for all phases of digestion. In addition, changes in the quantity of the assigned marker flavonoids (tiliroside, hyperoside and quercitrin) were monitored by High-Performance Thin Layer Chromatography (HPTLC) analysis. The antioxidant activity potentials of the extracts were studied by various methods to reveal their detailed activity profiles. On the other hand, in vitro α-amylase and α-glucosidase enzymes and advanced-glycation end product (AGE) inhibitory activities of the extracts were determined to evaluate the antidiabetic potentials of extracts. The results showed that aqueous extracts obtained from the aerial parts of Turkish Cistus species have rich phenolic contents and potential antioxidant and antidiabetic activities; however, their bioactivity profiles and marker flavonoid concentrations might significantly be affected by human digestion. The results exhibited that total phenolic contents, antioxidant activities and diabetes-related enzyme inhibitions of the bioavailable samples were lower than non-digested samples in all extracts.

Modulatory effects of laurel-leaf cistus (Cistus laurifolius) ethanolic extract on innate immune responses and disease resistance in common carp (Cyprinus carpio).

Medicinal herbs are used for growth promotion, disease control and other health benefits in aquaculture industry. Here, we examined the effect of dietary laurel-leaf cistus (Cistus laurifolius) ethanolic extract on growth performance, digestive enzyme activity, haematological profile and nonspecific immune responses in common carp (Cyprinus carpio). In addition, resistance against Aeromonas hydrophila infection was examined. Common carp was fed diets containing 0 (Control), 0.1 (CL0.1), 0.5 (CL0.5) and 1 (CL1) g kg-1 laurel-leaf cistus extract for 45 days. After 30 days, superoxide anion production (SAP) increased in CL0.1 and CL0.5 fish groups and at the end of the study all experimental fish groups had higher SAP compared to that of the control (P ˂ 0.05). Lysozyme activity (LA) was elevated in CL0.5 and CL1 treated groups on 30th day (P < 0.05), and this increase was only observed in C0.1 fish group at the end of study compared to control (P ˂ 0.05). Myeloperoxidase activity was significantly increased in CL0.5 and CL1 fish groups at the end of study. IL-1ßgene expression was significantly increased in treated fish in a dose-depended manner. Similar results were observed for transcription of IL-6 and IL-8 (P < 0.05). Anti-inflammatory cytokines, IL-10 and TGF-ß were highly up-regulated in the intestine and head kidney of CL treated fish groups compared to control (P < 0.05). At the end of experiment, significantly higher final body weight, weight gain, and specific growth rate were obtained in CL0.1 treated fish group compared to control. However, growth was negatively affected in CL1 fish group (P < 0.05). CL1 fish group had also a significantly higher FCR. Amylase activity was significantly increased in all experimental fish groups compared to control (P ˂ 0.05). Trypsin activity was decreased in CL0.1 and CL1 fish groups (P ˂ 0.05). WBC and RBC were significantly increased (P ˂ 0.05) in CL0.5 and CL1 fish groups, whereas haemoglobin, haematocrit, mean cell, mean cell haemoglobin contents were no significantly changed among control and treatment groups. Result of challenge test with A. hydrophila exhibited that survival rate in all treatment groups was significantly higher than that of control. These findings demonstrated that laurel-leaf cistus at 0.1 g kg-1 can be a suitable candidate for growth promotion, immune system induction and infection control in fish.

Essential Oils from Residual Foliage of Forest Tree and Shrub Species: Yield and Antioxidant Capacity.

Increasing applications and markets for essential oils could bring new opportunities for cost-effective and sustainable management of unused forestry biomass; however, better knowledge of the production and application of such essential oils is necessary. The objective of this work is to contribute to greater knowledge of the essential oil production on a pilot scale from foliage biomass of wild shrubs and tree residues produced in some forestry enhancement operations and to study their antioxidant capacity (ORAC-oxygen radical absorbance capacity). Fresh biomass (twigs) of seven species (E. globulus, E. nitens, P. pinaster, P. sylvestris, R. officinalis, C. ladanifer, and J. communis) was manually collected in Spain in two different periods and was ground at 30 mm and distilled in a 30 L stainless steel still with saturated steam. The essential oil components were identified by GC-MS and quantified by GC-FID, and their antioxidant activity was determined with the ORAC method. Promising results on essential oil yield were obtained with E. globulus, E. nitens, R. officinalis, and J. communis. All essential oils studied exhibited antioxidant capacity by the ORAC assay, particularly that from C. ladanifer. Moreover, oxygenated sesquiterpenes contents, one of the minor components of oils, were significantly correlated with ORAC values.

Comparative effects of metformin and Cistus laurifolius L. extract in streptozotocin-induced diabetic rat model: oxidative, inflammatory, apoptotic, and histopathological analyzes.

Interest in phytochemical therapy methods in the treatment of diabetes is increasing day by day. Although the antidiabetic and antioxidant effects of Cistus laurifolius L. (CL) have been mentioned, the systemic effects remain unknown. The present study aims at evaluating the antidiabetic effects of the CL aqueous extract via metformin on streptozotocin (STZ)-induced diabetic rats. Forty male Wistar albino rats were divided into five groups of eight animals each: control, diabetic group (55mg/kg STZ), STZ+125mg/kg CL, STZ+250mg/kg CL, and STZ+100mg/kg metformin. The effects of CL and metformin on oxidative, apoptotic, and inflammatory pathways were comparatively investigated. In addition, nuclear factor-κB (NFκB), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1ß expressions analysis were carried out. CL treatment resulted in a significant improvement in blood glucose levels, lipid profile, pancreatic markers, and liver and kidney function tests. A 250mg/kg CL treatment decreased by 67.9%, 31.6%, 66.8%, 28.3%, and 31.4% in the total oxidant capacity, NFκB, TNF-α, IL-1ß, caspase3, and cytochrome c levels, respectively, compared to the diabetic group. Additionally, CL treatments showed a dose-dependent reduction in NFκB, TNF-α, and IL-1ß expression levels. A 250mg/kg CL treatment exhibited a greater increase (by 9.6%) in total antioxidant capacity than metformin. CL treatment provided histologically more improvement in the brain, heart, pancreas, spleen, liver, kidney, and testicular tissues compared to the metformin group. Our results suggest that the single treatment of CL aqueous extract at the low doses may have stronger short-term anti-diabetic effects than metformin. Therefore, further studies are needed regarding the long-term hypoglycemic effect or treatment of CL aqueous extract.

Analytical Profiling of Phenolic Compounds in Extracts of Three Cistus Species from Sardinia and Their Potential Antimicrobial and Antioxidant Activity.

The Cistaceae family is well represented in Sardinia, and the Cistus genus is widely used in traditional medicine. Nowadays only few studies have been performed on this genus vegetating in Sardinia in spite of its ethnobotanical importance. Moreover, in the past there have been conflicting opinions among botanists for the exact assignment of the species growing in Sardinia. We started several years ago to carried out studies on this genus and in the present study was to evaluate the in vitro activity of several samples of Cistus salvifolius L., Cistus monspeliensis L., and Cistus albidus L. collected in Sardinia as antimicrobial agents against Escherichia coli, Staphylococcus aureus, and four Candida species and their antioxidant activity using DPPH, ABTS, and FRAP assays. Furthermore, the phenolic content and composition of the extracts were first evaluated. Using statistical multivariate analysis on the complete metabolomics profile of all Cistus species growing wild in Sardinia, we confirmed the botanical classification, and we observed an interesting correlation between metabolomics profile and antioxidant activity.

The antimicrobial capacity of Cistus salviifolius and Punica granatum plant extracts against clinical pathogens is related to their polyphenolic composition.

Antimicrobial resistance poses a serious threat to human health worldwide. Plant compounds may help to overcome antibiotic resistance due to their potential resistance modifying capacity. Several botanical extracts and pure polyphenolic compounds were screened against a panel of eleven bacterial isolates with clinical relevance. The two best performing agents, Cistus salviifolius (CS) and Punica granatum (GP) extracts, were tested against 100 Staphylococcus aureus clinical isolates, which resulted in average MIC50 values ranging between 50-80 µg/mL. CS extract, containing hydrolyzable tannins and flavonoids such as myricetin and quercetin derivatives, demonstrated higher activity against methicillin-resistant S. aureus isolates. GP extract, which contained mostly hydrolyzable tannins, such as punicalin and punicalagin, was more effective against methicillin-sensitive S. aureus isolates. Generalized linear model regression and multiple correspondence statistical analysis revealed a correlation between a higher susceptibility to CS extract with bacterial resistance to beta-lactam antibiotics and quinolones. On the contrary, susceptibility to GP extract was related with bacteria sensitive to quinolones and oxacillin. Bacterial susceptibility to GP and CS extracts was linked to a resistance profile based on cell wall disruption mechanism. In conclusion, a differential antibacterial activity against S. aureus isolates was observed depending on antibiotic resistance profile of isolates and extract polyphenolic composition, which may lead to development of combinatorial therapies including antibiotics and botanical extracts.

Linking jasmonates with vitamin E accumulation in plants: a case study in the Mediterranean shrub Cistus albidus L.

MAIN CONCLUSION: Jasmonic acid positively modulates vitamin E accumulation, but the latter can also partly influence the capacity to accumulate the jasmonic acid precursor, 12-oxo-phytodienoic acid, in white-leaved rockrose (Cistus albidus L.) plants growing in their natural habitat. This study suggests a bidirectional link between chloroplastic antioxidants and lipid peroxidation-derived hormones in plants. While vitamin E is well known for its antioxidant properties being involved in plant responses to abiotic stress, jasmonates are generally related to biotic stress responses in plants. Studying them in non-model plants under natural conditions is crucial for the knowledge on their relationship, which will help us to better understand mechanisms and limits of stress tolerance to implement better conservation strategies in vulnerable ecosystems. We studied a typical Mediterranean shrub, white-leaved rockrose (Cistus albidus) under natural conditions during three winters and we analyzed both α and γ-tocopherol, and the three main jasmonates forms 12-oxo-phytodienoic acid (OPDA), jasmonic acid (JA), and jasmonoyl-isoleucine (JA-Ile). We found that JA contents positively correlated with vitamin E accumulation, most particularly with γ-tocopherol, the precursor of α-tocopherol (the most active vitamin E form). This finding was confirmed by exogenous application of methyl jasmonate (MeJA) in leaf discs under controlled conditions, which increased γ-tocopherol when applied at 0.1 mM MeJA and α-tocopherol at 1 mM MeJA. Furthermore, a complementary meta-analysis study with previously published reports revealed a positive correlation between JA and vitamin E, although this relationship turned to be strongly species specific. A strong negative correlation was observed, however, between total tocopherols and OPDA (a JA precursor located in chloroplasts). This antagonistic effect was observed between α-tocopherol and OPDA, but not between γ-tocopherol and OPDA. It is concluded that (i) variations in jasmonates and vitamin E due to yearly, inter-individual and sun orientation-driven variability are compatible with a partial regulation of vitamin E accumulation by jasmonates, (ii) vitamin E may also exert a role in the modulation of the biosynthesis of OPDA, with a much smaller effect, if any, on other jasmonates, and (iii) a trade-off in the accumulation of vitamin E and jasmonates might occur in the regulation of biotic and abiotic stress responses in plants.

The effect of Cistus incanus herbal tea supplementation on oxidative stress markers and lipid profile in healthy adults.

BACKGROUND: Oxidative stress and dyslipidemia play a critical role in the development of cardiovascular disease (CVD). Regular intake of polyphenol-rich diets is associated with a reduced risk of CVDs. METHODS: The present study was a pilot study with 24 healthy volunteers and was designed to determine if a 12-week administration of Cistus incanus herbal tea, containing phenolic acids and flavonoids, reduces cardiovascular risk factors including oxidative stress and dyslipidemia in healthy adults. Phenolic compounds profile and antibacterial activity of Cistus incanus infusion were also measured. RESULTS: Herbal infusion led to improvement in lipid profile by increase (D4%, p = 0.033) high-density lipoprotein cholesterol concentration and decrease triglyceride (D14%, p = 0.013) concentrations. In addition, the Cistus incanus diet was associated with decreased serum concentrations of malondialdehyde (D16%, p < 0.01) and advanced oxidation protein products (D18%, p < 0.001). CONCLUSIONS: Cistus incanus administration decreases cardiovascular risk factors including oxidative stress and dyslipidemia and this action supports the idea of using Cistus incanus tea on a daily basis as an effective dietary component for prevention of atherosclerotic CVD.