Scientists headed by a team at the Innovative Academy of Seed Design, Chinese Academy of Sciences, have developed transgenic rice that contains multiple antihypertensive peptides (MAHPs) derived from food proteins. When given to hypertensive rats, the transgenic rice flour lowered the animals’ blood pressure, with no evidence of adverse developmental or other side effects on either hypertensive rats, or normal, wild-type (WT) rats.
The findings could mean that in the future, taking blood pressure-lowering medication might be as simple as eating a spoonful of rice. The antihypertensive peptides in rice might also have fewer side effects than current synthetic blood pressure medicines, the researchers suggested. The team, headed by Le Qing Qu, reported on the transgenic rice and initial in vivo tests in rats, in the ACS’ Journal of Agricultural and Food Chemistry, in an article titled, “Hypotensive Activity of Transgenic Rice Seed Accumulating Multiple Antihypertensive peptides.” In their paper, the scientists concluded, “The MAHPs produced by transgenic rice are expected to serve as alternatives to current antihypertensive agents.”
High blood pressure is a major risk factor for cardiovascular disease and stroke. Synthetic ACE inhibitor drugs that are commonly used to treat hypertension target angiotensin converting enzyme (ACE), which plays a crucial role in blood pressure regulation. However, these synthetic ACE inhibitors can cause unwanted side effects, such as dry cough, headache, skin rashes, and kidney impairment. In contrast, natural ACE inhibitors found in some foods, including milk, eggs, fish, meat, and plants, might have fewer side effects. “Known for having fewer side effects, these bioactive peptides could serve as alternatives to current antihypertensive medicines,” the authors wrote.
However, purifying large amounts of ACE-inhibitory peptides from foods is expensive and time-consuming, which is a major drawback to their widespread use. “ … as a result of the high cost associated with the multiple processing steps (i.e., fermentation and/or enzymatic digestion and purification) needed to produce peptides, usage of food-derived ACE inhibitory peptides is limited,” the team continued.
Le Qing Qu and colleagues set out to genetically modify rice—one of the world’s most commonly eaten foods—to produce a mixture of ACE-inhibitory peptides from other food sources. “Rice (Oryza sativa) is a staple food for more than half of the world’s population,” the investigators wrote. “Rice seed is also an ideal platform for the production of recombinant proteins, because it has a high yield, low growth cost, large storage ability, and high storage safety with respect to recombinant protein.”
The investigators designed a chimeric gene that codes for the amino acid sequences of nine ACE-inhibitory peptides (ACEIPs) and a blood vessel-relaxing peptide. They then introduced the gene into rice plants. After confirming that the plants made high levels of the peptides, the researchers extracted total protein (including the peptides) from the transgenic rice and administered the peptides intragastrically into spontaneously hypertensive rats (SHRs) and Wistar Kyoto normotensive rats (WNRs), which acted as the control animals. They found that two hours after treatment, the hypertensive animals showed a reduction in blood pressure, while rats treated with wild-type rice proteins did not. Blood pressure wasn’t affected in the control animals. “These results indicate that the MAHPs accumulated in the transgenic rice seed display obvious antihypertensive activity in SHRs but do not affect the blood pressure of WT rats,” the investigators stated.
Treatment of rats over a five-week period using flour from the transgenic rice also reduced blood pressure, and this effect remained one week later. The treated rats’ blood pressure was reduced by 6.2–32.8 mmHg during the experimental period. “Furthermore, for a period of five weeks, daily intragastric administration of the transgenic rice flour also significantly reduced the SBP of SHRs but not the Wistar Kyoto normotensive rats (WNRs), most importantly, which did not affect the growth, development, or serum chemistry of SHRs or WNRs and did not cause any pathological changes,” the investigators stated. “This suggested that the antihypertensive peptides were released into the rats in sufficient quantities.”
The researchers calculated that if these peptides have the same effects in humans, a 150-pound adult would need to eat only about half a tablespoon of the special rice daily to prevent and treat hypertension. “Thus, if translatable to humans, consuming ~7.5 g of the MAHP rice daily will meet the requirements for prevention and cure of hypertension for an adult weighing 70 kg … Our work provides an alternative source of natural antihypertensive agents,” they concluded. “The MAHP transgenic rice may serve as a novel ingredient in the development of functional food products used as dietary treatments for the prevention and cure of hypertension.”
