Researchers at Yonsei University College of Medicine and Pharmacy have found that punicalagin, a natural substance in the peel of a pomegranate, is effective in treating lupus nephritis intractable disease.
Lupus nephritis is nephritis caused by systemic lupus erythematosus invading the kidneys. Systemic lupus erythematosus is a representative autoimmune disease, in which the immune system that defends the human body from the outside causes an abnormality and attacks the human body.
The basic guide to the treatment of lupus nephritis is to use an injection of an anticancer agent (cyclophosphamide) or an oral immunosuppressant (mycophenolate or tacrolimus) based on adrenal cortical hormone (steroid).
However, 10-20 percent of patients with lupus nephritis type 4 who have poor prognosis have chronic renal failure or end-stage renal failure that requires dialysis within five years. Also, secondary complications may occur as a side effect of treatment, so there was an unmet medical need to develop an effective and safe treatment than the existing treatment.
To resolve such problems, the team, led by Professors Lee Sang-won, Namkung Wan, Mun Chin-hee, and Seo Yo-han at the hospital, focused on PAR2 receptors, one of the G-protein-coupled receptors, and natural substances to develop therapeutic agent.
The researchers noted that they chose the two substances as suppressing the PAR2 receptor is likely to relieve various inflammations, including arthritis, dermatitis, and vasculitis, including lupus nephritis, while natural substances have long been an essential source for drug development, are relatively safer than synthetic compounds.
Professor Namkung's team assessed more than 1,000 natural products using the high-throughput screening technique, which quickly and accurately evaluates the activity of substances using automated equipment.
As a result, the team discovered that punicalagin was capable of selectively inhibiting the PAR2 receptor even at low concentrations and had an excellent antioxidant effect.
Based on such findings, Professor Lee's team evaluated the efficacy of punicalagin in an animal model of lupus nephritis to confirm its potential as a therapeutic agent for lupus nephritis.
The research showed that punicalagin inhibited the production of inflammatory substances involved in the development and exacerbation of lupus nephritis in the kidney of the animal model of lupus nephritis, while the substance also produced elements that could relieve inflammation.
"The study suggested the possibility of developing a new, safer, and more effective treatment for lupus nephritis patients who were unable to receive adequate treatment due to side effects or ineffective treatments," Professor Lee said. "We will do our best to develop treatments for patients, and demonstrate the effectiveness of treatment by applying punicalagin to other rheumatoid diseases that affect the kidneys."
Professor Namkung also said, "This is a meaningful study that has established a foundation for developing new drugs based on natural products for patients with lupus nephritis who desperately need an effective and safe treatment."
As punicalagin is a relatively safe and human-friendly material, the team plans to continue its research to develop various treatments for inflammatory diseases, including lupus.