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In order to improve the hydrophobicity and volatility of terpinen-4-ol and extend its duration of action, β-cyclodextrin-based metal-organic framework (β-CD-MOF) was first prepared by the modified vapor diffusion method, and then terpinen-4-ol was encapsulated with the β-CD-MOF to prepare a terpinen-4-ol/β-CD-MOF inclusion complex by the solvent incubation method. The mass ratio of the prepared β-CD-MOF or β-CD used as the control to terpinen-4-ol was optimized for encapsulation. The morphological characteristics, spectral absorption properties and thermogravimetric characterisation of the terpinen-4-ol/β-CD-MOF complex were analyzed. Through in vitro bacteriostatic assays, the inhibitory effects of the complex on three food-borne pathogens were determined. The results showed that the highest drug loading and encapsulation efficiency were achieved when the mass ratio of terpinen-4-ol to β-CD-MOF was 1:1, superior to the same preparation conditions using β-CD as a carrier. Scanning electron microscope (SEM) observations indicated that irregularly arranged β-CD molecules stacked together under the bridging action of K+, forming an orderly arranged rectangular β-CD-MOF. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis demonstrated terpinen-4-ol was successfully encapsulated in β-CD-MOF with hydrogen bond interactions between them. Thermogravimetric analysis (TGA) proved that the volatilization rate of terpinen-4-ol could be retarded when encapsulated by β-CD-MOF, extending its application temperature range from 30~160 ℃ to 30~350 ℃. In vitro antibacterial experiments showed that the terpinen-4-ol/β-CD-MOF complex exhibited long-lasting antibacterial abilities against three common cold-chain microorganisms, including Escherichia coli, Staphylococcus aureus and Listeria monocytogenes. In conclusion, encapsulating terpinen-4-ol in β-CD-MOF allows for effective preservation, providing a theoretical basis for the development of novel, green and safe antimicrobial materials for cold-chain applications.

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To investigate the therapeutic effect of metronidazole gel combined with terpinen-4-ol on demodex blepharitis. Methods: 100 patients (100 eyes) with demodex blepharitis were divided into control group and study group according to the random number table method, 50 cases (50 eyes) in each group. Control group was treated with terpinen-4-ol cotton tablets, and study group was treated with metronidazole gel on the basis of control group. The changes of demodex mites microscopic examination counts, eye symptoms (itching, dryness, foreign body sensation, blurred vision) score, ocular surface related score [ocular surface disease index (OSDI) score, meibomian gland opening score], tear film stability index [tear film breakup time (BUT), corneal fluorescein staining (FL) score] were observed before and after treatment in two groups. Results: 1 month after treatment and 3 months after treatment, the demodex mites microscopic examination counts in two groups decreased, and study group was lower than that of control group at the same time point (P<0.05). 1 month after treatment and 3 months after treatment, the scores of eye itching, dryness, foreign body sensation, blurred vision, OSDI, meibomian gland opening and FL in two groups decreased, and study group were lower than those of control group at the same time point (P<0.05). 1 month after treatment and 3 months after treatment, BUT increased, and study group was higher than that of control group at the same time point (P<0.05). Conclusion: The curative effect of metronidazole gel combined with terpinen-4-ol in the treatment of demodex blepharitis is significant, which can strengthen the effect of mite removal, improve the stability of tear film and effectively reduce the eye symptoms of patients. [ABSTRACT FROM AUTHOR]

Objective To investigate the synergistic bacteriostatic effect of terpinen-4-ol (T4O) and α-bisabolol (Bis) on Staphylococcus aureus (S.aureus) and Cutibacterium acnes (C.acnes). Methods The microdilution checkerboard technique was used to determine the minimum inhibitory concentration (MIC) of T4O combined with Bis on the two etu perimental bacteria, and fractional inhibitory concentration index (FICI) was calculated. An MIC group (T4O and Bis at a concentration of MIC), a 2×MIC group (T4O and Bis at a concentration of 2×MIC), and a negative control group (no T4O or Bis added) were set up for each experimental bacterium; the time-bactericidal curve was plotted for each experimental bacterium after the addition of both T4O and Bis; each group of the two experimental bacteria was measured in terms of Zeta potential (ZP) on the surface of the strain, leakage of intracellular nucleic acid and protein, damage of bacterial biofilm, and respiratory chain dehydrogenase activity in S.aureus after the addition of both T4O and Bis; a transmission electron microscope was used to observe the influence of T4O combined with Bis on the morphology of the two experimental bacteria. Results The combination of T4O and Bis for S.aureus and C.acnes had an FICI of

BACKGROUND: Terpinen-4-ol has been found to have a significant antibacterial activity against pathogenic bacteria associated with peri-implantitis and can reduce the formation of surface biofilm and the occurrence of peri-implantitis when applied to the surface of titanium implants; however, the studies regarding its biosafety are lacking. OBJECTIVE: To explore the antibacterial effects of terpinen-4-ol on Staphylococcus aureus and Streptococcus mutans and its effect on the growth and osteogenic differentiation of MC3T3-E1 cells. METHODS: Different concentrations of terpinen-4-ol were dissolved in dimethyl sulfoxide. The minimum inhibitory concentration and minimum bactericidal concentration of pineolene 4 alcohol solution against Staphylococcus aureus and Streptococcus mutans were tested. The 1/2 minimum inhibitory concentration, minimum inhibitory concentration, and minimum bactericidal concentration of pineolene 4 alcohol were tested by bacteriostatic zone test. MC3T3-E1 cells were treated with different concentrations (0%, 0.3%, 0.2%, 0.1%, v/v) of terpinen-4-ol in medium or calcification-inducing solution. The proliferation activity of cells was detected by CCK-8 assay. Cells were stained with rhodamine-phalloidin to observe cytoskeleton. Differentiation ability of cells was detected by alkaline phosphatase activity assay. The formation of mineralized nodules was observed by alizarin red staining. The mRNA expression of Runx2 and osteocalcin was detected by real-time reverse transcription-polymerase chain reaction. RESULTS AND CONCLUSION: (1) Minimum inhibitory concentration and minimum bactericidal concentration of terpinen-4-ol against Streptococcus mutans were 0.1% (v/v) and 0.4% (v/v) respectively and against Staphylococcus aureus were 0.03% (v/v) and 0.125% (v/v) respectively. With the increase of the concentration of terpinen-4-ol, the diameter of bacteriostatic zone was significantly increased (P < 0.05). (2) CCK-8 assay showed that terpinen-4-ol promoted the proliferation of MC3T3-E1 cells, with the most obvious effects in the 0.2% group. (3) Rhodamine-phalloidin staining showed that terpinen-4-ol promoted the adhesion of MC3T3-E1 cells. (4) Alkaline phosphatase activity assay and alizarin red staining showed that terpinen-4-ol promoted the early differentiation and mineralization of MC3T3-E1 cells, with the most obvious effects in the 0.2% group. (5) Real-time reverse transcription-polymerase chain reaction showed that the mRNA expression of Runx2 was significantly higher in the 0.3%, 0.2%, and 0.1% groups than in the 0% group at 1 day of calcification induction (P < 0.05), and the mRNA expression of Runx2 and osteocalcin was significantly higher in the 0.2% and 0.1% groups than in the 0.3% and 0% groups at 7 and 14 days of calcification induction (P < 0.05). (6) These results indicate that terpinen-4-ol can inhibit the growth of Staphylococcus aureus and Streptococcus mutans and promote the proliferation, differentiation and mineralization of MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

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Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia , which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G&#95;1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G&#95;1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.