Berberine in Human Oncogenic Herpesvirus Infections and Their Linked Cancers.

Human herpesviruses are known to induce a broad spectrum of diseases, ranging from common cold sores to cancer, and infections with some types of these viruses, known as human oncogenic herpesviruses (HOHVs), can cause cancer. Challenges with viral latency, recurrent infections, and drug resistance have generated the need for finding new drugs with the ability to overcome these barriers. Berberine (BBR), a naturally occurring alkaloid, is known for its multiple biological activities, including antiviral and anticancer effects. This paper comprehensively compiles all studies that have featured anti-HOHV properties of BBR along with promising preventive effects against the associated cancers. The mechanisms and pathways induced by BBR via targeting the herpesvirus life cycle and the pathogenesis of the linked malignancies are reviewed. Approaches to enhance the therapeutic efficacy of BBR and its use in clinical practice as an anti-herpesvirus drug are also discussed.

Multiple In vitro biological effects of phenolic compounds from Morus alba root bark.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. is used in traditional Chinese medicine for the treatment of various diseases, including bacterial infections and inflammation. As a rich source of phenolic compounds, the plant is an object of many phytochemical and pharmacological studies. AIM OF THE STUDY: The aim of the study was to isolate and evaluate possible parallel antiviral, antibacterial, and anti-inflammatory activities of phenolic mulberry compounds. MATERIALS AND METHODS: Extensive chromatographic separation of mulberry root bark extract and in vitro biological screening of 26 constituents identified promising candidates for further pharmacological research. Selected compounds were screened for anti-infective and anti-inflammatory activities. Antiviral activity was determined by the plaque number reduction assay and by the titer reduction assay, antibacterial using broth microdilution method, and anti-inflammatory activity using COX Colorimetric inhibitor screening assay kit. One compound was evaluated in vivo in carrageenan-induced paw-edema in mice. RESULTS: Five prenylated compounds 1, 2, 8, 9, and 11, together with a simple phenolic ester 13, exhibited inhibitory activity against the replication of herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2), with IC50 values ranging from 0.64 to 1.93 µg/mL, and EC50 values 0.93 and 1.61 µg/mL. Molecular docking studies demonstrated the effects of the active compounds by targeting HSV-1 DNA polymerase and HSV-2 protease. In antibacterial assay, compounds 1, 4, 11, and 17 diminished the growth of all of the Gram-positive strains tested, with MIC values of 1-16 µg/mL. The anti-inflammatory ability of several compounds to inhibit cyclooxygenase 2 (COX-2) was tested in vitro, and compound 16 displayed greater activity than the indomethacin, positive control. Mulberrofuran B (11) showed anti-inflammatory activity in vivo against carrageenan-induced paw-edema in mice. CONCLUSIONS: Experimental investigation showed promising antiviral, antibacterial, and/or anti-inflammatory activities of the phenolic mulberry constituents, often with multiple inhibitory effects that might be used as a potential source of new medicine.

In Vitro Study of Multi-Therapeutic Properties of Thymus bovei Benth. Essential Oil and Its Main Component for Promoting Their Use in Clinical Practice.

Thymus bovei Benth. (TB) is an important plant in the traditional medicine of the Mediterranean region. This study investigates the health-promoting properties of TB essential oil (TB-EO) for its possible use in clinical practice with regards to its cytotoxic, anti-herpes simplex virus type 2 (HSV-2), and antihypertensive (through inhibition of human angiotensin-converting enzyme; ACE) properties. The phytochemical profile of EO (99.9%) was analyzed by Gas Chromatography with Flame-Ionization Detection (GC-FID) and Gas Chromatography-Mass Spectrometry (GC-MS). In this study, all biological methods were performed at the level of in vitro studies. The results showed that TB-EO exerted remarked cytotoxic properties against human cervical carcinoma cells, colon cancer cells, and lung adenocarcinoma cells with the half-maximal inhibitory concentration (IC50) values of 7.22, 9.30, and 8.62 µg/mL, respectively, in comparison with that of standard anticancer drug cisplatin with IC50 values of 4.24, 5.21, and 5.43 µg/mL, respectively. Fascinatingly, TB-EO showed very weak cytotoxicity on the healthy human fetal lung fibroblast cells with an IC50 value of 118.34 µg/mL compared with that of cisplatin (IC50 = 10.08 µg/mL). TB-EO, its main component geraniol, TB-EO combined with acyclovir (ACV) along with standard ACV, have displayed pronounced inhibitory properties against the replication of HSV-2 with the half-maximal effective concentration (EC50) values of 2.13, 1.92, 0.81 and 1.94 µg/mL, respectively, with corresponding selectivity indices (SI) 98.59, 109.38, 259.26 and 108.25, respectively. TB-EO and geraniol at a concentration of 15 µg/mL showed prominent inhibitory activities against ACE with % of inhibition 95.4% and 92.2%, respectively, compared with that of standard inhibitor captopril (99.8%; 15 µg/mL). Molecular docking studies were performed to unveil the mechanism of action of geraniol as well as structural parameters necessary for anti-HSV-2 activity (through the inhibition of HSV-2 protease) and ACE inhibition. This is the first report on the chemical composition of Egyptian TB-EO along with the above-mentioned biological activities. Our results may be considered as novel findings in the course of a search for new and active anticancer, anti-HSV-2 and antihypertensive agents, and expand the medicinal value of this plant and its phytochemicals in clinical practice.

Anti-Infectivity against Herpes Simplex Virus and Selected Microbes and Anti-Inflammatory Activities of Compounds Isolated from Eucalyptus globulus Labill.

Herpes simplex virus (HSV) causes numerous mild-to-serious human diseases, including mucocutaneous herpes infections and life-threatening herpes encephalitis. Moreover, herpes viral lesions can be complicated by inflammation and secondary bacterial infections. The development of resistance to antiviral drugs along with the undesirable side effects of these drugs are relevant argue for the development of new anti-HSV drugs with diverse mechanisms of action. Eucalyptus extracts have been used for decades to combat various infectious diseases. We isolated and studied 12 pure compounds and one mixture of two constitutional isomers from the leaves and twigs of E. globulus. The structures were identified by spectroscopic methods (NMR, HR-MS, IR) and all of them were tested for antiherpetic activity against the replication of antigen types HSV-1 and HSV-2. Tereticornate A (12) (IC50: 0.96 µg/mL; selectivity index CC50/IC50: 218.8) showed the strongest activity in the anti-HSV-1 assay, even greater than acyclovir (IC50: 1.92 µg/mL; selectivity index CC50/IC50: 109.4), a standard antiviral drug. Cypellocarpin C (5) (EC50: 0.73 µg/mL; selectivity index CC50/EC50: 287.7) showed the most potent anti-HSV-2 activity, also more intensive than acyclovir (EC50: 1.75 µg/mL; selectivity index CC50/EC50: 120.0). The antimicrobial activity of the isolated compounds was also evaluated against the bacteria Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa and the yeast Candida albicans. The anti-inflammatory potential was examined using LPS-stimulated THP-1-XBlue™-MD2-CD14 and THP-1 macrophages and focusing on the influences of the NF-κB/AP-1 activity and the secretion of pro-inflammatory cytokines IL-1ß and TNF-α.

Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay.

For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL-1, respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL-1. This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

Plumbagin, a Plant-Derived Compound, Exhibits Antifungal Combinatory Effect with Amphotericin B against Candida albicans Clinical Isolates and Anti-hepatitis C Virus Activity.

Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), the major active constituent of Plumbago indica L., has been shown to be effective against a wide range of infectious microbes. In this study, plumbagin has been evaluated in vitro for its antifungal combinatory effect with amphotericin B against Candida albicans (C. albicans) clinical isolates and anti-hepatitis C virus (HCV) activity. Antifungal activity was determined by broth microdilution method, and combinatory effect was evaluated by checkerboard assay according to ΣFIC indices, while cytotoxicity was determined by MTT assay. Anti-HCV activity was determined in infected Huh7.5 cells using quantitative real-time reverse transcription PCR, and cytotoxicity was evaluated by MTT assay. Plumbagin exerted inhibitory effect against all C. albicans strains with minimum inhibitory concentration values ranging from 7.41 to 11.24 µg/mL. The additive effect of plumbagin when combined with amphotericin B at concentrations of (0.12, 0.13 and 0.19, 1.81 µg/mL, respectively) was obtained against five of seven strains tested with ΣFIC ranging from 0.62 to 0.91. In addition, plumbagin was found to be used safely for topical application when combined with amphotericin B at concentrations corresponding to the additive effect. Plumbagin exerted anti-HCV activity compared with that of telaprevir with IC50 values of 0.57 and 0.01 µM/L, respectively, and selectivity indices SI = 53.7 and SI = 2127, respectively. Our results present plumbagin as a potential therapeutic agent in the treatment of C. albicans and HCV infections. Copyright © 2016 John Wiley & Sons, Ltd.