Peganum spp.: A Comprehensive Review on Bioactivities and Health-Enhancing Effects and Their Potential for the Formulation of Functional Foods and Pharmaceutical Drugs.

The genus Peganum includes four species widely distributed in warm temperate to subtropical regions from the Mediterranean to Mongolia as well as certain regions in America. Among these species, Peganum harmala L., distributed from the Mediterranean region to Central Asia, has been studied and its phytochemical profile, traditional folk use, and application in pharmacological and clinical trials are well known. The review is aimed at presenting an insight into the botanical features and geographical distribution of Peganum spp. along with traditional folk uses. This manuscript also reviews the phytochemical profile of Peganum spp. and its correlation with biological activities evidenced by the in vitro and in vivo investigations. Moreover, this review gives us an understanding of the bioactive compounds from Peganum as health promoters followed by the safety and adverse effects on human health. In relation to their multipurpose therapeutic properties, various parts of this plant such as seeds, bark, and roots present bioactive compounds promoting health benefits. An updated search (until December 2020) was carried out in databases such as PubMed and ScienceDirect. Chemical studies have presented beta-carboline alkaloids as the most active constituents, with harmalol, harmaline, and harmine being the latest and most studied among these naturally occurring alkaloids. The Peganum spp. extracts have shown neuroprotective, anticancer, antimicrobial, and antiviral effects. The extracts are also found effective in improving respiratory disorders (asthma and cough conditions), dermatoses, and knee osteoarthritis. Bioactivities and health-enhancing effects of Peganum spp. make it a potential candidate for the formulation of functional foods and pharmaceutical drugs. Nevertheless, adverse effects of this plant have also been described, and therefore new bioproducts need to be studied in depth. In fact, the design of new formulations and nanoformulations to control the release of active compounds will be necessary to achieve successful pharmacological and therapeutic treatments.

A mucoadhesive thermosensitive hydrogel containing erythropoietin as a potential treatment in oral mucositis: in vitro and in vivo studies.

Oral mucositis (OM) represents a therapeutic challenge frequently encountered in cancer patients undergoing chemotherapy or radiotherapy. Erythropoietin (EPO) has anti-inflammatory, antioxidant, and wound-healing properties and therefore has important roles in the prevention and treatment of OM. In the current study, we developed a thermally sensitive mucoadhesive gel based on trimethyl chitosan (TMC) containing EPO for the treatment of OM. TMCs with various degrees of substitution (DS) were synthesized and mixed with ß-glycerophosphate (GP) and characterized for gelation properties by means of rheological analysis. The effects of DS of TMCs and different concentrations of GP on gelation temperature and time were investigated. The mucoadhesive property of the mixtures was also assessed using cattle buccal mucosa. The optimized mixture was loaded with EPO and subjected to in vitro drug release, wash away, in vitro antimicrobial, and wound-healing tests. The effect of EPO-loaded formulation was also investigated in vivo in Sprague-Dawley rats with chemotherapy-induced mucositis. The best properties were obtained with the blend of TMC of 9.8% DS (5%) and GP (20%). EPO was released from the hydrogel during 8 h, and more than 30% of the drug still remained on the mucosa after 3 h of washing the buccal mucosa with phosphate buffer. TMC/GP mixture was characterized by antimicrobial properties. The EPO hydrogel demonstrated in vitro/in vivo wound-healing properties. Therefore, EPO-loaded hydrogel has the potential to be used in the treatment of OM and other oral or subcutaneous wounds.

Effect of freeze drying on stability, thermo-responsive characteristics, and in vivo wound healing of erythropoietin-loaded trimethyl chitosan/glycerophosphate hydrogel.

Erythropoietin (EPO) was successfully incorporated into a bioadhesive thermosensitive hydrogel based on trimethyl chitosan (TMC)/ß-glycerophosphate (GP) for prevention and treatment of oral mucositis in cancerous patients. The aim of the present study was to evaluate the effect of freeze drying on thermo-responsive property of the hydrogel and structural stability of the loaded protein. The freeze-dried EPO-loaded hydrogel were characterized using various methods. Gelation property by rheological analysis, EPO aggregation in formulations by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), protein secondary structure by far ultraviolet-circular dichroism (CD), and the antigenic activity of EPO with ELISA techniques. The healing effects of the freeze-dried formulation was also investigated in Sprague-Dawley rats with chemotherapy-induced mucositis and compared with freshly prepared mixture. Finally, the retention time of the gel in the oral cavity was assessed in healthy volunteers. SDS-PAGE, CD, and ELISA confirmed the stability of conformational structure of loaded and released EPO. Severity of mucositis was markedly reduced in animals treated with freeze-dried EPO hydrogel; whereas the group received normal saline did not show any significant healing. EPO salvia level was decreased rapidly following EPO solution compared to the gel application. Approximately, 40% of EPO was maintained on the buccal areas in patients receiving the hydrogel system after 30 min. Therefore, the TMC/GP could preserve EPO stability after freeze drying and has the potential in the treatment of oral mucositis and other oral or subcutaneous wounds.