Borneol exerts its antipruritic effects by inhibiting TRPA1 and activating TRPM8.

ETHNOPHARMACOLOGICAL RELEVANCE: Borneol is a long-established traditional Chinese medicine that has been found to be effective in treating pain and itchy skin. However, whether borneol has a therapeutic effect on chronic itch and its related mechanisms remain unclear. AIM OF THE STUDY: To investigate the antipruritic effect of borneol and its molecular mechanism. MATERIALS AND METHODS: DrugBAN framework and molecular docking were applied to predict the targets of borneol, and the calcium imaging or patch-clamp recording analysis were used to detect the effects of borneol on TRPA1, TRPM8 or TRPV3 channels in HEK293T cells. In addition, various mouse models of acute itch and chronic itch were established to evaluate the antipruritic effects of borneol on C57BL/6J mice. Then, the borneol-induced pruritic relief was further investigated in Trpa1-/-, Trpm8-/-, or Trpa1-/-/Trpm8-/- mice. The effects of borneol on the activation of TRPM8 and the inhibition of TRPA1 were also measured in dorsal root ganglia neurons of wild-type (WT), Trpm8-/- and Trpv1-/- mice. Lastly, a randomized, double-blind study of adult patients was conducted to evaluate the clinical antipruritic effect of borneol. RESULTS: TRPA1, TRPV3 and TRPM8 are the potential targets of borneol according to the results of DrugBAN algorithm and molecular docking. Calcium imaging and patch-clamp recording analysis demonstrated that borneol activates TRPM8 channel-induced cell excitability and inhibits TRPA1 channel-mediated cell excitability in transfected HEK293T cells. Animal behavior analysis showed that borneol can significantly reduce acute and chronic itch behavior in C57BL/6J mice, but this effect was eliminated in Trpa1-/-, Trpm8-/- mice, or at least in Trpa1-/-/Trpm8-/- mice. Borneol elicits TRPM8 channel induced [Ca2+]i responses but inhibits AITC or SADBE-induced activation of TRPA1 channels in dorsal root ganglia neurons of WT and Trpv1-/- mice, respectively. Furthermore, the clinical results indicated that borneol could reduce itching symptoms in patients and its efficacy is similar to that of menthol. CONCLUSION: Borneol has therapeutic effects on multiple pruritus models in mice and patients with chronic itch, and the mechanism may be through inhibiting TRPA1 and activating TRPM8.

Polymyxin E biomineralized and doxorubicin-loaded gold nanoflowers nanodrug for chemo-photothermal therapy.

Gold nanoparticles are a kind of good photothermal agents. However, gold nanoparticle photothermal agents have low photothermal conversion efficiency and low tumor inhibiting ability. To overcome these problems, polymyxin E (PE) biomineralized and doxorubicin-loaded gold nanoflowers (DOX-SH@AuNFs) nanodrug was synthesized by the green synthesis method using the biological antimicrobial peptide PE as a stabilizer and grower of crystal seed, and doxorubicin-thiol (DOX-SH) was further loaded on the gold nanoparticles through the Au-S bond. The final DOX-SH@AuNFs displayed a wide absorption band in the UV-Vis spectra, and their photothermal conversion efficiency was 33.9%. Furthermore, the inhibition rate of DOX-SH@AuNFs on A549 cells was as high as 80.1% under the irradiation of near-infrared light at 808 nm. The tumor inhibition rate of DOX-SH@AuNFs was as high as 87.81% in vivo experiments. The high tumor suppression rate was attributed to the high photothermal conversion ability of DOX-SH@AuNFs and the delivery of doxorubicin. Taken together, the method of preparing DOX-SH@AuNFs provides a new idea for the treatment of cancer by photothermal therapy and chemotherapy synergistic system.

Biomineralized synthesis of palladium nanoflowers for photothermal treatment of cancer and wound healing.

Photothermal therapy uses photothermal agents (PTAs) to convert light energy to heat energy under near-infrared light to kill local tumors in cancer patients or speed up wound healing in diabetic patients. However, it is difficult to achieve high photothermal conversion efficiency for most of PTAs. Herein, daptomycin (Dap) micelles-stabilized palladium nanoflowers (Dap-PdNFs) were prepared for the first time. The palladium nanoflowers (PdNFs) inside of the Dap-PdNFs were 106 nm. The temperature of the Dap-PdNFs solution quickly rose from 26.8 °C to 52.0 °C within 10 min under irradiation with high photothermal conversion efficiency up to 38%. In addition, the cell viability of HeLa cells and HT-29 cells of Dap-PdNFs exceeded 95% in the absence of near-infrared light, indicating that Dap-PdNFs had good biocompatibility. Meanwhile, the inhibition rate of Dap-PdNFs on HeLa cells was as high as 71.2% under irradiation of 808 nm near-infrared light. More importantly, Dap-PdNFs had a good healing effect on wounds of diabetic mice under irradiation of 808 nm near-infrared light. In short, this research provides a facile method for the application of Dap-PdNFs in safe and efficient tumor treatment and wound healing.

Synthesis of gold nanoflowers stabilized with amphiphilic daptomycin for enhanced photothermal antitumor and antibacterial effects.

The development of effective agents for cancer therapy and inhibition of bacterial infection has drawn a great deal of interest. Photothermal therapy has been widely used for the thermal ablation of tumor cells. In addition, antibiotics have the ability to inhibit the growth of bacteria. Thus, the combination of photothermal therapy and antibiotics may be one of the methods to address the problem. Herein, it is the first time that daptomycin (Dap) micelles were used as the template and reducing agents to prepare stable daptomycin-gold nanoflowers (Dap-AunNFs) under mild conditions. The energy dispersive spectrometer (EDS) spectrum and X-ray diffraction (XRD) spectrum indicated that Dap-AunNFs were successfully prepared. When the molar ratio of HAuCl4 to Dap was 6, the gold nanoparticles inside of Dap-AunNFs were about 80 nm with flower-like shape. In addition, the photothermal conversion efficiency of Dap-Au6NFs was about 40%. More importantly, Dap-Au6NFs inhibited the growth of tumors and bacteria under the radiation of near-infrared light at 808 nm. The prepared Dap-Au6NFs could be used as photothermal antitumor and antibacterial agents in the future.

The Efficacy and Safety of a Herbal Toothpaste in Reducing Gingivitis: A Double-Blind, Randomized, Placebo-Controlled, Parallel Allocation Clinical Trial.

AIM: To examine the efficacy and safety of the toothpaste containing Rhizoma Chuanxiong and Rhizoma Imperatae extracts in reducing gingivitis. METHOD: A double-blind clinical trial was conducted, in which 120 volunteers were randomly assigned to the test group (N = 60) or the control group (N = 60). Tetramethylpyrazine, senkyunolide A, ferulic acid, and ligustilide are the main effective components of Rhizoma Chuanxiong and Rhizoma Imperatae contains the main components of cylindrin, carotene, 5-hydroxytryptamine, potassium, and calcium. The control group used placebo toothpaste containing neither Rhizoma Chuanxiong extract nor Rhizoma Imperatae extract. Plaque, gingivitis, and bleeding were assessed at the baseline, prior to the supragingival scaling, and at 4, 8, and 12 weeks. RESULTS: During the trial, both test and control groups showed a decreasing trend compared to the baseline. At the end of 12 weeks, with respect to Gingival Index (GI), Bleeding Index (BI), and Bleeding on Probing percentage (BOP%) scores, there were significant differences between test and control groups (GI, P<0.001, BI, P<0.001, and BOP%, P<0.001, resp.). After 4 weeks of usage, there were no statistically significant differences in all of GI, BI, and BOP% scores between the two groups. However, the decrease became statistically significant at next two intervals (GI, P<0.001, BI, P<0.001, and BOP%, P<0.001, resp.) in the efficiency of GI, BI, and BOP% which was 8.04%, 11.02%, and 37.16%, respectively. There were no treatment-related adverse events reported. CONCLUSION: The toothpaste containing Rhizoma Chuanxiong and Rhizoma Imperatae extracts was well tolerated and significantly reduced gingivitis and bleeding after usage for 12 weeks. There was better improvement at molars, and the more serious the baseline status was, the better the efficacy was.

Metabolic profile of 5-hydroxy-4-methoxycanthin-6-one, a typical canthinone alkaloid, in rats determined by liquid chromatography-quadrupole time-of-flight tandem mass spectrometry together with multiple data processing techniques.

Picrasma quassioides (D. Don) Benn. is a traditional Chinese medicine used clinically to treat gastrointestinal disorders and as a vermifuge. 5-Hydroxy-4-methoxycanthin-6-one (CAN), a major canthinone alkaloid found in P. quassioides, has significant pharmacological activities. In the present study, a method using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry together with multiple data processing techniques, including extracted ion chromatogram, multiple mass defect filter, precursor/product ion scanning and neutral loss scanning was developed to screen and characterize the phase I and II metabolites of CAN in plasma, bile, urine and feces of rats after a single oral dose of 20mg/kg. A total of 17 metabolites were tentatively or conclusively identified. Pathways for the metabolism of CAN have been proposed, and include hydroxylation, N-decarbonylation, methylation, oxidation and sequential conjugation. A previously unknown metabolically active site at the C4-C6 position and a novel N-decarbonylation-oxidation metabolic pathway for the prototypical canthinone alkaloid, CAN, were discovered. Our results provide valuable information about the in vivo metabolism of CAN that can also be used as a comprehensive guide for the biotransformation of other canthinone alkaloids.

Cannabisin B induces autophagic cell death by inhibiting the AKT/mTOR pathway and S phase cell cycle arrest in HepG2 cells.

This study investigates the anticancer properties of cannabisin B, purified from hempseed hull, in HepG2 human hepatoblastoma cells. The results indicate that cannabisin B significantly inhibited cell proliferation by inducing autophagic cell death rather than typical apoptosis. Cell viability transiently increased upon the addition of a low concentration of cannabisin B but decreased upon the addition of high concentrations. Cannabisin B-induced changes in cell viability were completely inhibited by pre-treatment with 3-methyladenine (3-MA), indicating that the induction of autophagy by cannabisin B caused cell death. Additionally, cannabisin B induced S phase cell cycle arrest in a dose-dependent manner. Moreover, cannabisin B was found to inhibit survival signaling by blocking the activation of AKT and down-stream targets of the mammalian target of rapamycin (mTOR). These findings suggest that cannabisin B possesses considerable antiproliferative activity and that it may be utilised as a promising chemopreventive agent against hepatoblastoma disease.

The isolation and identification of two compounds with predominant radical scavenging activity in hempseed (seed of Cannabis sativa L.).

Forty samples were extracted from defatted kernels and hulls of two varieties of hempseed (Bama and Yunma No. 1) using 10 different polar solvent systems. The radical scavenging capacity of the extracts was evaluated using 2,2-diphenyl-1-pikrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays and the total phenolic content was determined by Folin-Ciocalteu's phenol reagent. The correlation analysis indicated that the antioxidants in hempseed belonged to phenolic and DPPH() assay was suitable for evaluating the radical scavenging activity. Two compounds, with predominant antiradical activity, were isolated in 60% ethanol extract of hempseed hull using macroporous resin absorption, LH-20 gel chromatography, and high performance liquid chromatography methods, which were identified as N-trans-caffeoyltyramine and cannabisin B by high-resolution mass spectra, nuclear magnetic resonance spectra, and ultraviolet data. The two compounds exhibited significant high DPPH() scavenging activity and protective effect against in vitro oxidation of human low-density lipoprotein compared with extracts from flaxseed, grape seed, and soybean. This suggests that hempseed hull extract is a potential source of natural antioxidants, which could be added to dietary supplements to help prevent oxidative stress.

Analytical characterization of Hempseed (seed of Cannabis sativa L.) oil from eight regions in China.

In this study, eight cultivars of hempseed were collected from different regions of China for analysis of physiochemical properties and chemical composition, as well as for seed indexes and proximate composition of seed kernel. The results indicated that Yunma No. 1 and Bama Huoma, with more than 50% oil and 30% protein in dehulled seed, could be considered as oil extraction material and protein source with respect to kernel yield. Iodine values ranging from 153.6 to 169.1 g/100 g reflected the high degree of unsaturation. The concentration of unsaturated fatty acids exceeded 90%, higher than most conventional vegetable oils. Moreover, polyunsaturated fatty acids ranged from 76.26% to 82.75% and were mainly composed of linoleic acid and α-linolenic acid with a ratio close to 3:1. γ-Tocopherol was found at an average concentration of 28.23 mg/100 g of hempseed oil. The results indicated that hempseed oil is a potentially valuable vegetable oil.