No abstract

Key factors in compromised wound healing primarily include bacterial colonization and infection. Extensive use of systemic antibiotics, preferred choice of treatment for clinically infected wounds, is often accompanied with emergence of bacterial resistance. Quorum sensing (QS), density dependent chemical communication, is emerging as a promising area of research since most infectious microorganisms operate this mechanism to realize their pathogenic potential. Foregoing research indicates the potential of studying medicinal plant extracts/components and their combinations as vital inhibitors of QS regulated virulence factors’ production. Our study aims to understand the potential of three plant extracts and their combinations as vital inhibitors of QS regulated virulence factor’s production by two wound pathogens and to achieve this our objectives are to perform their violacein inhibitory (on C. violaceum) and biofilm inhibitory properties (on Pseudomonas aeruginosa and Staphylococcus aureus). Minimum inhibitory concentration (MIC) of aqueous plant extracts against P aeruginosa and S aureus was performed (two-fold serial microdilution). Violacein inhibition was assayed using agar well diffusion while biofilm inhibition by crystal violet method. Organisms presented 5mg/ml (Bacopa monnieri ), 2.5mg/ml (Acalypha indica), and 2.5mg/ml (Calotropis gigantea) as MIC. Three sets of individual extract concentrations (sub-MIC in μg/ml) and their corresponding combinations were used for this study. Extracts exhibited more significant (P<0.0001) violacein inhibition in combination than individually. Biofilm inhibition by extracts' combination was also significantly (P<0.001) higher than that of individual extracts indicating a possible positive herb-herb interaction of phytoconstituents (synergistic or complementary). The relative decrease in response to individual extracts in higher concentrations (set 'c') by both organisms point to possible recalcitrance behavior generally exhibited by bacteria on exposure to higher antibacterial agents. The improved antibiofilm efficacy exhibited by this novel combination may serve as an alternative approach in managing wound colonization by biofilm-producing bacteria and hence faster-wound healing.

The Bacopa monnieri plant contains a large repertoire of active phytochemicals that have been used extensively in traditional medicine for the treatment of various complex diseases. More recently it has been shown to increase the wound healing rate in rats, though its mechanism of action is largely unknown. Here we investigated the cellular pathways activated by a methanol extract of Bacopa monnieri in human dermal fibroblasts, which play many critical roles in the wound healing program. Gene expression analysis revealed that Bacopa monnieri extract can enhance tissue repair by modulating multiple processes involved in the wound healing program such as migration, proliferation, and angiogenesis. We discovered that Bacopa monnieri extract can increase migration of fibroblasts via modulating the size and number of focal adhesions. Bacopa monnieri-mediated changes in focal adhesions are dependent on alpha5beta1 integrin activation and subsequent phosphorylation of Focal Adhesion Kinase (FAK). Altogether our results suggest that Bacopa monnieri extract could enhance the wound healing rate via modulating fibroblast migration in the wound bed.

Wound healing still remains as an unmet therapeutic challenge and a significant clinical and economic burden among medical society even with considerable research on advanced wound care globally. Myriads of wound healing products and strategies are currently available. Some of these products are synthetic chemical moieties like chlorhexidine, betadine etc with systemic side effects such as crystalluria, methaemoglobinaemia, renal impairment, ototoxicity and renal/thyroid dysfunctions. Even the advanced wound healing therapy such as bioengineered cellular wound therapies and stem cells therapies come with some disadvantages such as unaffordability to common man and difficulty in obtaining sufficient stem cells due to their low regenerative potential and ethical issues. The shortcomings associated with current available wound healing strategies necessitated the increasing interest in the use of medicinal plants in wound management. The growing interest towards medicinal plants primarily resulted as an outcome of scientific advancement in delineating the principles and molecular mechanisms behind the contribution of various phytoconstituents in them. Meticulous combination of several medicinal plants in the form of polyherbal formulations (PHFs) such as Ankaferd, herboheal and Ari’s wound healing cream are reported to be safe and provide effective wound healing compared to the use of single plant. Several reviews on wound healing properties of individual plants and PHFs have been reported, but the multitargeted, synergistic and the complementary contributions of individual phytoconstituents in the PHFs at different complex stages of wound healing need to be given the desired attention. The aim of this review is to provide together a comprehensive report on the latent potentials of the positive herb-herb combination as a promising approach to wound healing. Our objective is to systematically collect research, and review articles from various open access research databases and study them to bring out the salient features of PHFs in relation to the effective wound management. A composite drug approach such as PHF is a better treatment option for improved wound management as many phytoconstituents in it can synergistically tackle multiple wound healing processes simultaneously. They are reported to be effective on multidrug resistant bacteria by inhibiting the complex quorum sensing regulated virulence factors’ production and eventually causing their death. Transformations of active phytoconstituents that are reported to occur in PHFs may lead to formation of novel pharmacologically active compound/s, and nanoparticle/s. These transformations may lead to discovery of novel wound healing drug/s that researchers and pharmaceutical industries need to pay more attention to.