The Role of Plant MicroRNAs in Herbal Medicine

Might some of the effects of herbal medicines also be ascribed to plant microRNAs? For example, thousands of microRNAs have been identified in ginseng. Based on their sequences, they could theoretically in turn affect thousands of human genes, but they have yet to be tested. Others have been, however. Synthetic microRNAs based on sequences recovered from licorice tea were evidently found to have anti-inflammatory effects in human cells, which could help explain why multiple randomized controlled trials have shown that gargling with licorice a few minutes before general anesthesia can decrease the incidence of postoperative sore throat due to the placement of the breathing tube.

A meta-analysis of more than a hundred randomized controlled trials of a traditional Chinese herbal medicine known as red sage or danshen suggests a benefit for treating angina chest pain superior to the pharmaceutical isosorbide dinitrate, a slow-acting nitroglycerine-type drug sold as Isordil. Two recent studies found that microRNAs from the plant show direct cardioprotective properties, though they were both performed in mice. The most striking such finding to date was on another traditional Chinese herb, honeysuckle.

Honeysuckle tea has long been used in the Chinese culture to combat cold and flu symptoms. Various active components have been isolated over the years to account for its purported benefit for respiratory infections. But researchers recently discovered an atypical microRNA in the tea that peaks in the bloodstream of mice at about six hours after ingestion that appeared to bind directly to the influenza virus. When put to the test, it inhibited viral replication and dramatically reduced mouse mortality caused by infection with the bird flu virus H5N1. In the control group given “placebo” RNA, 100 percent of the mice died within two weeks. However, 75 percent of the infected mice given the tea survived, and more than 60 percent survived just given the microRNA alone. To underscore the importance of the microRNA, if you give infected mice the tea but also a microRNA silencer (the complementary sequence to bind up the microRNA), nearly 90 percent of the mice die. So, when COVID hit, they tried out the honeysuckle microRNA on people.

In vitro, the honeysuckle microRNA cuts the replication of SARS-CoV-2, the virus responsible for COVID-19, by more than 90 percent. To see if enough ended up in people’s bloodstream to have an inhibitory effect, the researchers exposed infected cells to the blood of volunteers before and after drinking a cup (240 ml) of honeysuckle tea. The honeysuckle microRNA levels were undetectable before the tea, but they jumped up to levels high enough to significantly suppress SARS-CoV-2 replication. The only step that remained is to actually try it out on infected patients. A pilot study of 75 hospitalized patients with moderate COVID were split into two groups. One group got about a half cup (120 ml) of strong honeysuckle tea twice a day and the other a traditional Chinese medicine mixture without honeysuckle. In a week, more than 80 percent of the honeysuckle group had cleared their infection, versus only about a quarter in the non-honeysuckle group, becoming PCR-negative after an average of 4 days instead of 12.

Unfortunately, like so many impromptu pandemic trials, the study left a lot to be desired. It’s not clear how, or even if, the patients were randomized, and only six ended up in the honeysuckle group. The control group was given some undefined herbal mixture that for all we know made things worse (potentially only making the honeysuckle look good in comparison). And even if the tea did actually work, unlike in the mouse study, the clinical study doesn’t tell us what role, if any, the microRNA played, compared to other honeysuckle components. Still, it represents an exciting avenue for exploration.

MicroRNAs may help explain how plants can be so powerful. Of course, while they could help explain why some medicinal herbs are so medicinal, they could also help explain why some poisonous plants are so poisonous. The neurotoxic effects of Atropa belladonna, also known as deadly nightshade, may be enhanced by a microRNA in the plant that appears to target an important human brain protein. The powerful effects of plants are not necessarily positive.