Research progress on synergistic reduction of bacterial resistance by plant active ingredients and antibiotics
Antibiotics were one of the greatest discoveries in medicine at the beginning of the 20th century and were widely used for the treatment of infectious diseases. However, with the long-term and irrational use of antibiotics, most susceptible bacteria have developed resistance to antibiotics. Once bacteria develop resistance to certain antibiotics, they can not only pass on this trait to their offspring through vertical gene transfer, but also transmit it to other bacteria through horizontal gene transfer. The genetic structure of drug-resistant bacteria changes so rapidly that the effectiveness of common antibiotics may be lost within 5 years. The main global strategies to address the challenges posed by bacterial resistance include strengthening resistance monitoring, rational use of antibiotics, development of new antibiotics, and restoration or enhancement of the antibacterial activity of existing antibiotics. The development and implementation of new drugs is a difficult, time-consuming, and expensive process, and new drug research and development cannot keep up with changes in bacterial resistance. As of now, the goal of successfully developing new drugs is far from being achieved. Therefore, restoring or enhancing the sensitivity of drug-resistant bacteria to existing antibiotics is an effective measure to control the continued development of bacterial resistance.

Plant active ingredients have antibacterial, antioxidant, anti-inflammatory and other effects, as well as advantages such as not easily developing drug resistance, fast metabolism in the body, low toxicity and no residue. Plant active ingredients, when used alone or in combination with antibiotics, have a wide range of antibacterial effects. When used in combination with antibiotics, they can effectively restore or enhance the antibacterial activity of existing antibiotics against resistant bacteria, providing a new strategy for reducing bacterial resistance. This article provides a review of the current status of bacterial resistance, the synergistic effects of plant active ingredients and antibiotics on drug-resistant bacteria, and their mechanisms, aiming to provide a theoretical basis for the application of plant active ingredients in reducing bacterial resistance.

Due to the irrational and excessive use of antibiotics, the problem of bacterial resistance is becoming increasingly serious and threatening global life safety. Plant active ingredients, such as alkaloids, polyphenols, terpenes, etc., although known and unknown antibacterial activities, have a relatively long period of antibacterial activity when used alone, weak antibacterial activity, and high dosage, which may lead to the accumulation of compounds in the body and cause poisoning or organ damage. Therefore, in clinical practice and animal husbandry, the combination of plant active ingredients and antibiotics is developed into synergistic antibacterial agents, restoring the sensitivity of drug-resistant bacteria to antibiotics, reducing the dosage of antibiotics and plant active ingredients, and reducing the potential toxic side effects caused by antibiotics and plant active ingredients, achieving the strategic goal of reducing resistance.

Plant active ingredients can enhance the antibacterial activity of conventional antibiotics by changing the target of antibiotics, inhibiting the activity of antibiotic hydrolysis/modification enzymes, promoting membrane permeability/inhibiting the activity of efflux pumps, and other mechanisms of action, providing a feasible strategy for solving the problem of bacterial resistance. Although plant active ingredients can synergistically inhibit bacteria with antibiotics through different mechanisms of action, there are differences in the metabolism of antibacterial agents in the human and animal bodies, and the reactions of humans and animals to antibacterial agents are also different. Therefore, the standards for developing antibacterial agents by synergistically using plant active ingredients with medical antibiotics are relatively stricter. Therefore, for the future development of synergistic antibacterial agents, dose-response (pharmacological), toxicity, and pharmacokinetic studies on experimental and target animals should be conducted first. Based on the pharmacological effects, toxicity, and pharmacokinetic characteristics shown in animal experiments, human clinical trials should be conducted. In clinical practice, its effectiveness is evaluated through pharmacokinetic characteristics, half-life, target organ aggregation degree, tissue distribution characteristics, etc., and its safety is evaluated through pharmacological interactions, pharmacokinetic interactions, etc., in order to ensure the safe and widespread application of synergistic antibacterial agents in clinical practice and animal husbandry. In the future, further exploration of the synergistic antibacterial mechanism between plant active ingredients and antibiotics and detection of residual antibacterial agents are of great significance for the development of new, efficient, and safe synergistic antibacterial agents.