In the 'no resistance' era, citral is promising!

Antibiotics are not only the "life-saving straw" for mankind, but also the "deadly killer" for mankind. The advent of antibiotics not only saved tens of thousands of lives, but also an important guarantee for the sustainable development of mankind. With the continuous proliferation of antibiotics, the follow-up problems caused by antibiotics gradually appear, and the abuse of antibiotics has become one of the serious burdens of society.

The continuous emergence of drug-resistant bacteria and super bacteria is a typical adverse consequence of human application of antibiotics. It not only complicates the treatment of human diseases, but also consumes too many social resources. Substitutes and reductions have become the development of the antibiotic era. Main melody.


Severe abuse and tighter policies

It is reported that the average annual consumption of antibiotics per capita in my country is 138g, which is more than 10 times that of the United States. The abuse of human antibiotics is very prominent. To this end, the country has successively promulgated the "Opinions on Strengthening the Management of Pharmaceutical Affairs in Medical Institutions to Promote the Rational Use of Drugs" and the "National Action Plan for Containing Bacterial Resistance (2016-2020)" and other guidelines.

In July 2020, the National Health Commission issued the "Notice on Continued Management of the Clinical Application of Antimicrobial Drugs" to control the abuse of antibiotics from multiple dimensions.

The human health problems caused by the abuse of antibiotics in animal husbandry are more serious. The annual use of antibiotics in my country's animal husbandry production accounts for about 30% of the global antibiotic use. Although the country is actively pursuing the policy of reducing antibiotics, the control of antibiotics has always been more severe due to the restriction of low intensification. Studies have pointed out that about 60%-85% of antibiotics used in animals will be directly or indirectly gathered at the top of the biological chain in the form of prototypes, which will eventually lead to chronic harm to the human body. In recent years, the School of Public Health of Fudan University has conducted a survey of thousands of children aged 8-11 and 516 pregnant women. The results show that a total of 21 human, veterinary, or human and veterinary antibiotics were detected in children’s urine samples, and 79.6% of school-age children One or several antibiotics were detected in urine, some of which have been banned clinically.

In 2015, my country officially started the "ban on resistance" of animal husbandry. Lomefloxacin, pefloxacin, ofloxacin, and norfloxacin began to be completely banned from use in food animals.

The Ministry of Agriculture and Rural Affairs issued the "Announcement on Stopping the Production, Import, Operation, and Use of Certain Medicinal Feed Additives" (No. 194) in July 2019, clarifying that from July 1, 2020, feed manufacturers will stop producing The commercial feed of growth-promoting drug feed additives (except traditional Chinese medicine) has entered the era of "anti-resistance" in animal husbandry.


Alternatives need to be broken

Foreign countries started early in the research and development of antibiotic substitutes, and a variety of antibacterial products such as microecological preparations, antibacterial peptides, plant extracts, plant essential oils, and Chinese herbal medicines have come out one after another. However, there is still a big gap between the alternatives on the market and the antibiotics in terms of antibacterial scope and effect. It is difficult to achieve the actual expectations with a single or a simple combination of multiple types. The development of highly effective antibacterial agents is the core link of the current antibiotics.

Antibiotic substitutes have two notable features. First, they are green. They will not cause drug dependence and toxic side effects on animals, nor will they have enrichment effects on humans. As far as possible, use natural and harmless degradable ingredients. ；

Secondly, it must have a broad-spectrum and significant antibacterial effect, which can have significant antibacterial effects on a variety of bacteria.

Take potassium diformate as an example. It is the first feed additive approved by the European Union to replace antibiotics. Toxicity experiments show that the acute toxicity level of potassium diformate is very low. Reasonable use will not cause any toxic effects on consumers and operators. And within the specified dosage range, the only potassium diformate residue that can be detected in animal products is formate.

It reduces the pH value of the gastrointestinal tract, regulates the microbial flora of the digestive tract, reduces the number of pathogenic bacteria such as E. coli and Salmonella, and inhibits the reproduction of harmful bacteria, thereby promoting growth. Potassium diformate is a conventional indirect antibiotic substitute. my country formally approved potassium diformate for feed in 2005.


Citral has excellent antibacterial effect

In recent years, plant-derived active substances have received extensive attention due to their natural, safe and nutritious advantages, and they have also shown extremely high development value in antibacterial aspects.

Citral is the main active ingredient of lemongrass oil and Litsea cubeba oil, and it is widely present in plants. Studies have pointed out that citral has shown high bacteriostasis and safety in animal and human experiments. It is resistant to Staphylococcus aureus, Escherichia coli, Proteus, Enterococcus, Enterobacter sakazakii, Neisseria gonorrhoeae and white Candida, etc. have strong antibacterial activity.


Citral can also increase the sensitivity of pathogenic bacteria to antibiotics.

Antibiotics are the conventional treatment for Enterobacter sakazaki, but long-term antibiotic treatment increases the resistance of Enterobacter sakazaki, which not only reduces the therapeutic effect, but also increases the chance of infection. Studies have pointed out that citral can enhance the sensitivity of Enterobacter sakazaki to ampicillin and cefoxitin at sub-inhibitory concentrations, and is linearly related to the concentration, and has synergy with medicinal antibiotics effect. At the same time, animal experiments have confirmed that citral can significantly reduce the overall oxygen consumption of mice, optimize animal myocardial ischemic symptoms and inhibit platelet aggregation. It is a multifunctional antibacterial agent.

In practical applications, citral is mainly used in food flavoring due to its unique smell. my country and the European Union have included it in the ranks of flavors and fragrances. The US Food and Drug Administration has listed it as a generally recognized safe food ingredient. It is used in a variety of foods, which indirectly proves the safety of citral as a substitute for antibiotics.

However, citral also has a few adverse effects in its application. For example, studies have shown that a small dose of 2-5 mg of citral in monkeys can increase intraocular pressure, and serious cases may develop secondary glaucoma. The European Union also stipulates that citral is an allergen in cosmetics, and when it exceeds the specified content, it must be marked on the product label. It can be seen that there is still insufficient data to support the dose and effect of citral. But it has to be admitted that in the field of antibacterial, citral is a potential high-efficiency antibacterial agent, and will play a pivotal role in the future "anti-resistant" era.