Abstract

Piper cubeba is an important plant commonly known as cubeb or Java pepper, and it is cultivated for its fruit and essential oils, largely used to treat various diseases. Up to today, there was no scientific report on wound healing activity. Thus, this study was initiated to evaluate for the first time the antimicrobial activity and wound healing potential of a new chemotype from Piper cubeba essential oil (PCEO) from fruits. Thirteen microbial strains have been selected to investigate the antimicrobial potential of PCEO. For the evaluation of the wound healing potential, sixteen rats were excised on the dorsal back and divided into four groups. The effect of PCEO on the malondialdehyde (MDA) and superoxide dismutase (SOD) activities in the healed wound area of rats and the biochemical parameters and skin histological analysis were also assessed. Results: Data showed that PCEO exhibited a powerful antimicrobial potential especially against Listeria monocytogenes and Staphylococcus aureus. In addition, the topical application of PCEO cream appears to increase the SOD level, wound healing and contraction but reduced the MDA amount suggesting an impressive and a rapid cutaneous healing power. Additionally, histopathological analysis of the granulation tissue revealed that the derma is properly restored and arranged after treatment with PCEO. The docking analysis of PCEO constituents against S. aureus tyrosyl-tRNA synthetase enzyme showed binding energies values in the range of −7.2 to −4.8 kcal/mol. In conclusion, the topic use of PCEO healing cream showed significant effect in accelerating the healing process, which may be attributed to the synergetic effect of antioxidant and antimicrobial properties of PCEO volatile constituents, making it a relevant therapeutic agent for the management of wounds and therefore confirming the popular traditional uses of this plant.

Highlights

  • The oxidative stress (as the results of elevated intracellular levels of reactive oxygen species (ROS)) along with redox signaling play a substantial role in regulating normal wound healing under pathological conditions [1]

  • In light of the above facts and in the continuation of our investigations into Piper cubeba essential oil (PCEO) with therapeutic properties and limited data on this spice, we have studied for the first time the effects of its essential oil on wound healing and its antimicrobial activities against a wide range of strains supported by in silico study

  • Continuous to our previous work on the effectiveness of PCEO, GC–MS analyses have been already carried out recently by our team and here we are only able to present the structure of the identified compounds, which will be used for biological activities and Plants 2021, 10, 205

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Summary

Introduction

The oxidative stress (as the results of elevated intracellular levels of reactive oxygen species (ROS)) along with redox signaling play a substantial role in regulating normal wound healing under pathological conditions [1]. ROS are centrally involved and having a significant role in the orchestration of the normal wound-healing response acting as cellular messengers to many immunocytes and non-lymphoid cells [1,2]. They directly damage microbes that invade tissues and are known to play a pivotal role in regulating healing at low concentrations [2]. The hydrogen peroxide (H2 O2 ) produced by dismutation of superoxide acts as intracellular messengers with low concentrations (100–250 μM) by stimulating key phases of wound healing including cell recruitment, production of cytokines and angiogenesis, excessive and uncontrolled amount of ROS generation have deleterious effects by accelerating the non-healing wounds [4,5,6,7,8]. Several treatments are available for the wound management such as analgesics, antibiotics and nonsteroidal anti-inflammatory drugs, but most of them produce numerous unwanted side effects [8,20]

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