An Insight into Emerging Phytocompounds for Glioblastoma Multiforme Therapy.

Despite intense research in the field of glioblastoma multiforme (GBM) therapeutics, the resistance against approved therapy remains an issue of concern. The resistance against the therapy is widely reported due to factors like clonal selection, involvement of multiple developmental pathways, and majorly defective mismatch repair (MMR) mediated by O6- methylguanine DNA methyltransferase (MGMT). Phytotherapy is one of the most effective alternatives to overcome resistance. It involves plant-based compounds, divided into several classes: alkaloids; phenols; terpenes; organosulfur compounds. The phytocompounds comprised in these classes are extracted or processed from certain plant sources. They can target various proteins of molecular pathways associated with the progression and survival of GBM. Phytocompounds have also shown promise as immunomodulatory agents and are being explored for immune checkpoint inhibition. Therefore, research and innovations are required to understand the mechanism of action of such phytocompounds against GBM to develop efficacious treatments for the same. This review gives insight into the potential of phytochemical-based therapeutic options for GBM treatment.

Comparative analysis of α-pinene alone and combined with temozolomide in human glioblastoma cells.

α-Pinene (PEN) is a phyto compound present in terpene plants. In traditional medicine, PEN has been used for its anti-inflammatory, pain-relieving, and bronchodilator properties. The effect of PEN in combination with temozolomide (TMZ) in glioblastoma multiforme (GBM) cells has been evaluated. The action of the PEN + TMZ combination on cell migration, soft-agar, and cell death was determined in LN229 and U87MG human glioblastoma cells. In combination, PEN with TMZ showed a synergistic inhibitory effect in the GBM cells. The PEN + TMZ treatment showed a higher fluorescent intensity and reduced the percentage of wound area closure compared to the compound alone. The compounds in combination also resulted in a reduction in single-cell colony formation. To conclude, the study showed that plant-derived PEN enhanced the effectiveness of standard chemotherapeutic, TMZ, in LN229 and U87MG cells.

Nanoemulsions of Green Tea Catechins and Other Natural Compounds for the Treatment of Urinary Tract Infection: Antibacterial Analysis.

Purpose: Nanoemulsions (NEs) of polyphenon 60 (P60) and cranberry (NE I) and P60 and curcumin (NE II) were prepared with the aim to enhance anti-bacterial potential and to understand the mechanism of anti-bacterial action of the encapsulated compounds. Methods: To evaluate the antibacterial potential of the developed NE, microtiter biofilm formation assay was performed. The cytotoxicity analysis was done to assess the toxicity profile of the NEs. Further antibacterial analysis against uropathogenic strains was performed to check the developed NEs were effective against these strains. Results: In microtiter dish biofilm formation assay, both NE formulations inhibited the growth more effectively (Av. % inhibition ~84%) as compared to corresponding aqueous solution (Av. % inhibition ~64%) and placebo (Av. % inhibition ~59%) at their respective minimum inhibitory concentration (MIC) values. Cytotoxicity analysis using 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT assay) showed that the formulations were nontoxic to Vero cells. The antibacterial studies against uropathogenic resistant strains also showed that NEs effectively inhibited the growth of bacterial strains. Conclusion: From different studies it was concluded that both the NE's were able to inhibit bacterial strains and could be further used for the treatment of urinary tract infection (UTI). The antibacterial activity of developed NEs showed that these could be used as alternative therapies for the treatment of UTI.

Intravaginal Delivery of Polyphenon 60 and Curcumin Nanoemulsion Gel.

Polyphenon 60 (P60) and curcumin (CUR) were loaded in a single nanoemulsion system and their combined antibacterial action was studied against uropathogenic Escherichia coli. To enhance availability at target organs and to inhibit enzymatic degradation in gastro intestinal tract, vaginal route of administration was explored. P60 + CUR nanoemulsion (NE) was formulated by ultra-sonication and optimized using Box-Behnken design. Optimized NE showed Z-average of 211.2 nm, polydispersity index of 0.343, and zeta potential of -32.7 mV. Optimized P60+ CUR NE was characterized by stability testing and transmission electron microscopy, and it was observed that NE was stable at 4°C for 30 days and monodisperse in nature with particle size of 195-205 nm. P60+ CUR NE was further formulated as gel and characterized by viscosity, growth curve analysis, and in vitro permeation studies. In vitro drug permeation studies in simulated vaginal media showed maximum permeation (84 ± 0.21%) of curcumin within 5 h and (91 ± 0.16%) of P60 within 8 h. Both the drugs maintained sustained permeation for 12 h. To investigate the transport via intravaginal route, gamma scintigraphy and biodistribution study of P60 + CUR NBG was performed on Sprague-Dawley rats using 99mtechnetium pertechnetate for radiolabeling to P60 molecule. Following intravaginal administration, P60 + CUR NBG dispersed in the kidney and urinary bladder with (3.07 ± 0.15) and (3.35 ± 0.45) percentage per gram after 3 h for P60 and CUR, respectively, and remained active for 12 h. Scintigraphy images suggested that the P60 + CUR NBG given by intravaginal route led to effective distribution of actives in urinary tract, and this observation was in agreement with the biodistribution results.

Therapeutic effects of EGCG: a patent review.

INTRODUCTION: Green tea contains polyphenolic flavanoids such as epigallocatechin-3- gallate (EGCG), epicatechin-3-gallate (ECG), epigallocatechin (EGC) and epicatechin (EC). EGCG is the most abundant and active compound in green tea. Extensive research has shown that it has significant antioxidant, anti-carcinogenic, anti-microbial, and neuroprotective properties and has therapeutic potential against various human diseases. AREAS COVERED: This review focuses on the applications of EGCG alone, and in combination with other compounds, for the treatment of various types of cancers, metabolic, neurodegenerative, and microbial diseases, and discusses its mechanism of action in cell line and animal modesl. Recent advances, which include the use of nanoencapsulated EGCG to enhance the drug delivery and reduce cell toxicity, have also been discussed along with the comprehensive analysis of the specific granted patents associated with EGCG. EXPERT OPINION: Under the current scenario, the role of EGCG as a therapeutic agent is being utilised and new approaches are being formulated to overcome the problem of stability and bioavailability of EGCG. EGCG and its derivatives could be used for the development of drugs for the treatment of cancer, as well as various microbial, metabolic, and neurodegenerative diseases.

Green tea extract: possible mechanism and antibacterial activity on skin pathogens.

Camellia sinensis (tea) is known for its therapeutic properties (anti-inflammatory, anti-microbial, anti-tumour, anti-oxidative and anti-ageing). Although, anti-microbial properties of green tea have been studied, its role against bacterial strains related to skin infections and mechanism of action is not well understood. We focussed on exploring anti-microbial activity and the basic mechanism of aqueous green tea leaf extract on selected bacterial strains. Staphylococcus epidermidis, Micrococcus luteus, Brevibacterium linens, Pseudomonas fluorescens and Bacillus subtilis were found to be sensitive to green tea extract via disc diffusion assay (zone of inhibition ≥7 mm). Minimal inhibitory concentration (MIC) was determined via nitro blue tetrazolium (NBT) assay (0.156-0.313 mg/ml). Moreover, the aqueous extract was found to be not toxic to the Vero cell-line up to a concentration of 500 µg/ml. The effect of aqueous extract on adhesion of different bacteria to Vero cells indicated that it inhibits the adhesion at its MIC value.