Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection

The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have also spurred the re-examination of the potential of natural substances contained in Cannabis sativa L. Cannabinoids, apart from CB1 and CB2 receptors, may act multifacetedly through a number of other receptors, such as the GPR55, TRPV1, PPARs, 5-HT1A, adenosine and glycine receptors. The complex anti-inflammatory and antiviral effects of cannabinoids have been confirmed by interactions with various signaling pathways. Considering the fact that the SARS-CoV-2 virus causes excessive immune response and triggers an inflammatory cascade, and that cannabinoids have the ability to regulate these processes, it can be assumed that they have potential to be used in the treatment of COVID-19. During the pandemic, there were many publications on the subject of COVID-19, which indicate the potential impact of cannabinoids not only on the course of the disease, but also their role in prevention. It is worth noting that the anti-inflammatory and antiviral potential are shown not only by well-known cannabinoids, such as cannabidiol (CBD), but also secondary cannabinoids, such as cannabigerolic acid (CBGA) and terpenes, emphasizing the role of all of the plant’s compounds and the entourage effect. This article presents a narrative review of the current knowledge in this area available in the PubMed, Scopus and Web of Science medical databases.     

Protective Immunity against Listeria monocytogenes in Rats,Provided by HCl- and NaOH-Induced Listeria monocytogenes Bacterial Ghosts (LMGs) as Vaccine Candidates

Listeria monocytogenes (Lm) bacterial ghosts (LMGs) were produced by the minimum inhibitory concentration (MIC) of HCl, H₂SO₄, and NaOH. Acid and alkali effects on the LMGs were compared by in vitro and in vivo analyses. Scanning electron microscope showed that all chemicals form lysis pores on the Lm cell envelopes. Real-time qPCR revealed a complete absence of genomic DNA in HCl- and H₂SO₄-induced LMGs but not in NaOH-induced LMGs. HCl-, H₂SO₄- and NaOH-induced LMGs showed weaker or missing protein bands on SDS-PAGE gel when compared to wild-type Lm. Murine macrophages exposed to the HCl-induced LMGs showed higher cell viability than those exposed to NaOH-induced LMGs or wild-type Lm. The maximum level of cytokine expression (TNF-α, iNOS, IFN-γ, and IL-10 mRNA) was observed in the macrophages exposed to NaOH-induced LMGs, while that of IL-1β mRNA was observed in the macrophages exposed to HCl-induced LMGs. To investigate LMGs as a vaccine candidate, mice were divided into PBS buffer-injected, HCl- and NaOH-induced LMGs immunized groups. Mice vaccinated with HCl- and NOH-induced LMGs, respectively, significantly increased in specific IgG antibodies, bactericidal activities of serum, and CD4⁺ and CD8⁺ T-cell population. Antigenic Lm proteins reacted with antisera against HCl- and NOH-induced LMGs, respectively. Bacterial loads in HCl- and NaOH-induced LMGs immunized mice were significantly lower than PBS-injected mice after virulent Lm challenges. It suggested that vaccination with LMGs induces both humoral and cell-mediated immune responses and protects against virulent challenges.     

酚酸类化合物在化妆品中的研究进展

简单介绍了酚酸类化合物的来源和生物活性,综述了酚酸类化合物作为一种天然化合物,通过清除自由基、抑制炎症反应、抑菌、抑制酪氨酸酶活性、加速分解肌肤中的晚期糖化终末产物等途径起到的美白淡斑、抗衰老、抗炎、屏障修护等多重护肤功效,并介绍了酚酸类化合物的安全性问题,提出了酚酸类化合物生物利用度低、低水溶性等实际应用问题,采用生物基纳米颗粒负载酚酸类化合物可使部分实际应用问题得到改善。最后阐述了目前酚酸类化合物在化妆品行业应用中存在的问题,以期为酚酸类化合物在护肤领域的应用提供参考。     

Meloxicam affects the inflammatory responses of bovine mammary epithelial cells

Nonsteroidal anti-inflammatory drugs are used as supportive therapy with antimicrobial treatments for mastitis in cows to alleviate pain of the inflamed mammary gland. They act mainly by inhibition of cyclooxygenases. Meloxicam (MEL) is a drug designed for cyclooxygenase-2 selectivity, which is upregulated upon inflammation, acting as a key enzyme for the conversion of arachidonic acid to prostaglandins. Although some studies in dairy cows showed positive results in recovery from mastitis when MEL was added to the treatments, direct effects of MEL on the immune system of mastitic cows are unknown. The aim of this study was to investigate effects of MEL on the immune response of bovine mammary epithelial cells (MEC) with or without simultaneous immune stimulation by pathogen-associated molecular patterns of common mastitis pathogens. Mammary epithelial cells from 4 cows were isolated and cultured. To evaluate dose effects of MEL, MEC were challenged with or without 0.2 µg/mL lipopolysaccharide (LPS; serotype O26:B6 from Escherichia coli) with addition of increasing concentrations of MEL (0, 0.25, 0.5, 1.0, 1.5, or 2.0 mg/mL). The addition of MEL prevented the increase of mRNA expression of key inflammatory factors in LPS-challenged MEC in a dose-dependent manner. To investigate the effects of MEL on pathogen-specific immune responses of MEC, treatments included challenges with LPS from E. coli and lipoteichoic acid from Staphylococcus aureus with or without 1.5 mg/mL MEL for 3, 6, and 24 h. Meloxicam prevented the increase of mRNA abundance of key inflammatory mediators in response to LPS and lipoteichoic acid, such as tumor necrosis factor, serum amyloid A, inducible nitric oxide synthase, and the chemokines IL-8 and CXC chemokine ligands 3 and 5. The prostaglandin E₂ synthesis in challenged and nonchallenged cells was reduced by MEL within 24 h. Furthermore, MEL reduced the viability and consequently the total RNA yield of the cells. However, mRNA abundance of apoptosis-related enzymes was not affected by any treatment. Meloxicam had clear dose-dependent effects on the immune response of MEC to pathogen-associated molecular patterns of common mastitis pathogens by preventing increased expression of important factors involved in inflammation. This nonsteroidal anti-inflammatory drug also has detrimental effects on cell viability. How these effects would influence the elimination of pathogens from an infected mammary gland during mastitis therapy with meloxicam needs to be further investigated.     

Enhancement of nutraceutical properties of licorice callus cultures using sample pre-treatment strategy

Licorice is an herbal plant in the Leguminosae family, and its roots and rhizomes are used as sweeteners in food and confectionery products. Moreover, it has a distinct inflammatory activity. In the present study, a sample pre-treatment method to induce the deglycosylation of active metabolites in callus cultures of Glycyrrhiza inflata (GI) and Glycyrrhiza glabra (GG) was developed. The results of the method evaluation showed the biotransformation of ononin to formononetin, a rare flavonoid found in trace amounts in licorice. The magnitude of enhancement was 3- and 19-fold in the GI and GG samples, respectively. Moreover, the anti-inflammatory activity assay showed that the potency of the sample pre-treatment group was higher than that of the untreated group because it exerted an enhanced suppression of cyclo-oxygenase 2 (COX-2), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) gene expression. This is the first report on the anti-inflammatory activity of licorice callus, which has the potential to be utilised as a functional food for health promotion. These findings support the idea of using sample preparation to impart nutraceutical properties to plant products.