Biological and Pharmacological Properties of Myrtenol: A Review.

Myrtenol (C10H16O) is a volatile compound belonging to the terpenoid family of monocyclic monoterpenes. It is one of the essential oils constituents of several aromatic plants, including the genera Myrtus, Tanacetum, Artemisia, Hyssopus, and Rhodiola. The oxidation of α-pinene can produce it. Several reports demonstrated the pharmacological properties of myrtenol, including its antioxidant, antibacterial, antifungal, antidiabetic, anxiolytic, and gastroprotective activities. In this review, we discussed and highlighted in depth the pharmacological activities, cellular and molecular, providing insight into the mechanisms of myrtenol. In light of this finding, the interesting biological activities and abundance of myrtenol in nature suggests its potential applications in medicinal settings in the fight against various diseases.

Inhibition of Acanthamoeba polyphaga by chlorhexidine-mediated oxidative stress response.

OBJECTIVES: Acanthamoeba keratitis is a severe corneal infection caused by a ubiquitous opportunistic protozoan pathogen known as acanthamoeba. For the last decade, the approach to treating this infection typically includes the use of polyhexamethylene biguanide (0.02%) and/or chlorhexidine (Chx) (0.02%). Although chlorhexidine is reportedly effective, its mode of action towards this type of cell is not clear. The aim of this work was to study the effect of chlorhexidine on the oxidative status of Acanthamoeba polyphaga. METHODS: The effect of chlorhexidine (Chx) on the oxidative state of Acanthamoeba polyphaga was studied using different antiradical methods including ABTS, DPPH and FRAP and measuring the activity of a couple of antioxidant enzyme namely SOD, NADH-FRD and SDH. RESULTS: The chlorhexidine was able to induce oxidative imbalance in cells by over expression of reactive oxygen species and/or inhibiting the antioxidant enzymes. In addition to enhancing the antiradical activity in response to oxidative stress, the present drug was able to reduce the activity of two antioxidant enzymes, superoxide dismutase (SOD) and reduced flavin adenine dinucleotide-fumarate reductase (NADH-FRD), to 30% and 40%, respectively. CONCLUSIONS: We could observe an increase of the antiradical capacity of cell's lysate supernatant, to cope with the overproduction of ROS. The imbalance state The inhibition of both SOD and NADH-FRD activities could have a major role in cell oxidative imbalance.

The Role of Epigenetic Modifications in Human Cancers and the Use of Natural Compounds as Epidrugs: Mechanistic Pathways and Pharmacodynamic Actions.

Cancer is a complex disease resulting from the genetic and epigenetic disruption of normal cells. The mechanistic understanding of the pathways involved in tumor transformation has implicated a priori predominance of epigenetic perturbations and a posteriori genetic instability. In this work, we aimed to explain the mechanistic involvement of epigenetic pathways in the cancer process, as well as the abilities of natural bioactive compounds isolated from medicinal plants (flavonoids, phenolic acids, stilbenes, and ketones) to specifically target the epigenome of tumor cells. The molecular events leading to transformation, angiogenesis, and dissemination are often complex, stochastic, and take turns. On the other hand, the decisive advances in genomics, epigenomics, transcriptomics, and proteomics have allowed, in recent years, for the mechanistic decryption of the molecular pathways of the cancerization process. This could explain the possibility of specifically targeting this or that mechanism leading to cancerization. With the plasticity and flexibility of epigenetic modifications, some studies have started the pharmacological screening of natural substances against different epigenetic pathways (DNA methylation, histone acetylation, histone methylation, and chromatin remodeling) to restore the cellular memory lost during tumor transformation. These substances can inhibit DNMTs, modify chromatin remodeling, and adjust histone modifications in favor of pre-established cell identity by the differentiation program. Epidrugs are molecules that target the epigenome program and can therefore restore cell memory in cancerous diseases. Natural products isolated from medicinal plants such as flavonoids and phenolic acids have shown their ability to exhibit several actions on epigenetic modifiers, such as the inhibition of DNMT, HMT, and HAT. The mechanisms of these substances are specific and pleiotropic and can sometimes be stochastic, and their use as anticancer epidrugs is currently a remarkable avenue in the fight against human cancers.

Pharmacological Effects of Grifolin: Focusing on Anticancer Mechanisms.

Grifolin is a volatile compound contained in essential oils of several medicinal plants. Several studies show that this substance has been the subject of numerous pharmacological investigations, which have yielded interesting results. Grifolin demonstrated beneficial effects for health via its multiple pharmacological activities. It has anti-microbial properties against bacteria, fungi, and parasites. In addition, grifolin exhibited remarkable anti-cancer effects on different human cancer cells. The anticancer action of this molecule is related to its ability to act at cellular and molecular levels on different checkpoints controlling the signaling pathways of human cancer cell lines. Grifolin can induce apoptosis, cell cycle arrest, autophagy, and senescence in these cells. Despite its major pharmacological properties, grifolin has only been investigated in vitro and in vivo. Therefore, further investigations concerning pharmacodynamic and pharmacokinetic tests are required for any possible pharmaceutical application of this substance. Moreover, toxicological tests and other investigations involving humans as a study model are required to validate the safety and clinical applications of grifolin.

Isolation, identification, and activity evaluation of antioxidant components from Inula viscosa: A bioguided approach.

Oxidative stress is linked to several invasive diseases which causes significant clinical and economic impact, therefore, there is a need to develop new antioxidants. The natural products could play an important role in overcoming the current need. In the present work, the antioxidant bioassay-guided fractionation of the ethanolic extract of Inula viscosa leaves (Asteraceae) was performed using DPPH and ABTS assays affording three known compounds, which were successfully characterized as ilicic acid (1), taxifolin (2) and quercetin (3) based on 1D, 2D NMR. Compounds 2 and 3 were identified as the most active, displaying similar or higher potency against ABTS (value 41.27 for quercetin and 142.58 for taxifolin) and similar activity against DPPH (value 41.27 for quercetin and 142.58 for taxifolin) than the well-known reference, ascorbic acid (value 65.36 for quercetin and 58.43 for taxifolin) but less potency than the standard gallic acid. The discussion of SAR of the antioxidant potential revealed that the type of natural product is crucial for the activity and the substitution pattern on the flavonoid skeleton modulate the antioxidant profile. Our findings show that I. viscosa leaves may be a natural source of antioxidants and once again the role of flavonoids health benefits is more strongly endorsed.

Bioguided Isolation of Active Compounds from Rhamnus alaternus against Methicillin-Resistant Staphylococcus aureus (MRSA) and Panton-Valentine Leucocidin Positive Strains (MSSA-PVL).

Despite intensified efforts to develop an effective antibiotic, S. aureus is still a major cause of mortality and morbidity worldwide. The multidrug resistance of bacteria has considerably increased the difficulties of scientific research and the concomitant emergence of resistance is to be expected. In this study we have investigated the in vitro activity of 15 ethanol extracts prepared from Moroccan medicinal plants traditionally used for treatment of skin infections. Among the tested species I. viscosa, C. oxyacantha, R. tinctorum, A. herba alba, and B. hispanica showed moderate anti-staphylococcal activity. However, R. alaternus showed promising growth-inhibitory effects against specific pathogenic bacteria especially methicillin-susceptible Staphylococcus aureus Panton-Valentine leucocidin positive (MSSA-PVL) and methicillin-resistant S. aureus (MRSA). The bioguided fractionation of this plant using successive chromatographic separations followed by nuclear magnetic resonance (NMR) and mass spectrometry (MS) including EIMS and HREIMS analysis yielded the emodin (1) and kaempferol (2). Emodin being the most active with MICs ranging between 15.62 and 1.95 µg/mL and showing higher activity against the tested strains in comparison with the crude extract, its mechanism of action and the structure-activity relationship were interestingly discussed. The active compound has not displayed toxicity toward murine macrophage cells. The results obtained in the current study support the traditional uses of R. alaternus and suggest that this species could be a good source for the development of new anti-staphylococcal agents.

Exploring the Anti-Infective Value of Inuloxin A Isolated from Inula viscosa against the Brain-Eating Amoeba (Naegleria fowleri) by Activation of Programmed Cell Death.

Primary amoebic meningoencephalitis (PAM), caused by the pathogenic free-living amoeba Naegleria fowleri, is a rare but fatal disease. Nowadays, no fully effective therapy is available to erradicate or prevent this disease. Natural products could constitute a promising source of useful bioactive compounds in drug discovery. The present study is a characterization of main active compounds from the ethanolic extract of Inula viscosa (Asteraceae) leaves against N. fowleri trophozoites. Four compounds (1-4) were successfully identified by spectroscopic techniques, but only inuloxin A displayed a potential antiamoebic activity with an IC50 of 21.27 µM. The specificity of this compound toward the studied strain leads us to analyze the insight into its mechanism of action by performing in vitro assays of programmed cell death markers and to discuss the structure-activity relationship (SAR). The obtained results demonstrated that inuloxin A interferes with various processes leading to membrane damage, mitochondria alteration, chromatin condensation, and ROS accumulation, which highlight features specific to apoptosis. The current findings could be a promising step for developing new effective drugs against PAM.

Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids.

Neglected tropical diseases such as leishmaniasis and American trypanosomiasis represent an increasing health problem. Current treatments are not satisfactory which remains an urgent need for novel, cheap and safe chemotherapies. In the course of our ongoing search for new potential anti-protozoal agents, this study aimed to perform a bio-guided fractionation of Inula viscosa (Asteraceae) using in vitro assays against three strains of Leishmania and Trypanosma genus. Eight known compounds were identified from the ethanolic extract of leaves, sesquiterpenoids (3 and 4) and flavonoids (5 and 6) were characterized as the main bioactive constituents. Sesquiterpene lactones 3 and 4 (IC50 values between 4.99 and 14.26 µM) showed promising antiparasitic activity against promastigotes of L. donovani, L. amazonensis and epimastigotes of T. cruzi. Their structures were successfully characterized by spectroscopic techniques including 1D and 2D NMR experiments. Furthermore, the main bioactive compounds 4, 5 and 6 displayed higher potency (IC50 values between 0.64 and 2.13 µM) against amastigotes of L. amazonensis than miltefosine (IC50 3.11 µM), and a low toxicity on macrophages cell line (SI > 45). The analysis of structure-activity relationship (SAR) of the anti-protozoal activity revealed that lactonization or oxidation enhanced the biological profile, suggesting that the hydrophobic moiety was presumably involved in the activity by increasing the affinity and/or cell membrane permeability. In order to get an insight into the mechanism of action of these compounds, programmed cell death (PCD) experiments were performed, and the obtained results suggest that the reported compounds induced PCD in the treated parasites. These results highlight that sesquiterpenoids and flavonoids from I. viscosa could constitute an interesting scaffold for the development of novel antikinetoplastid agents.

From Wuhan to COVID-19 Pandemic: An Up-to-Date Review of Its Pathogenesis, Potential Therapeutics, and Recent Advances.

The emergence of a novel human coronavirus (SARS-CoV-2) causing severe contagious respiratory tract infections presents a serious threat to public health worldwide. To date, there are no specific antiviral agents available for this disease, currently known as COVID-19. Therefore, genomic sequencing and therapeutic clinical trials are being conducted to develop effective antiviral agents. Several reports have investigated FDA-approved drugs as well as in silico virtual screening approaches such as molecular docking and modeling to find novel antiviral agents. Until now, antiparasitic drugs such as chloroquine have shown the most relevant results. Furthermore, there is an urgent need to understand the pathogenesis of this novel coronavirus, its transmission routes, surface survival and evolution in the environment. So far, the scientific community has indicated a possible transmission of COVID-19 via blood transfusion which is challenging in the case of asymptomatic individuals. Protocols for pathogen inactivation are also needed. In this paper, we reviewed recent findings about this life-threatening pandemic.

Antistaphylococcal Activity and Phytochemical Analysis of Crude Extracts of Five Medicinal Plants Used in the Center of Morocco against Dermatitis.

Novel drugs for methicillin-resistant Staphylococcus aureus (MRSA) hospital- and community-acquired infections are needed because of the emergence of resistance against antibiotics. In this study, methanolic and aqueous extracts of Berberis hispanica, Crataegus oxyacantha, Cistus salviifolius, Ephedra altissima, and Lavandula dentata selected from an ethnopharmacological study to treat skin infections in Sefrou city (Center of Morocco) were tested for their antistaphylococcal activity against strains often involved in cutaneous disorders: two methicillin-resistant Staphylococcus aureus strains and one strain of Staphylococcus epidermidis using the well-diffusion assay, while the agar macrodilution method was used to determine the minimal inhibitory concentrations. The total phenolic compounds and flavonoid contents of all tested extracts were also evaluated. Three of the five methanolic extracts showed an important antibacterial activity. Berberis hispanica extract was the most active with a minimal inhibitory concentration of 04.00 mg/ml against all tested strains, followed by Cistus salviifolius and Crataegus oxyacantha extracts containing the highest amounts of total phenols (133.83 ± 9.03 and 140.67 ± 3.17 µg equivalent of gallic acid/mg of extract). However, the aqueous extracts have not shown any activity against the tested strains. The current data suggested that the most active extracts can be a good source of natural antistaphylococcal compounds and warrants further investigations to isolate bioactive molecules.