The phytochemical Isorhamnetin could be harnessed to treat Kidney Fibrosis

Herbs And Phytochemicals: In a recent breakthrough, researchers have discovered that a naturally occurring flavonoid, isorhamnetin (ISO), could potentially serve as a powerful agent against kidney fibrosis. This discovery offers new hope for patients suffering from chronic kidney disease (CKD), where renal fibrosis plays a crucial role in disease progression. This Herbs And Phytochemicals news report delves into the findings of the study and explores how isorhamnetin might revolutionize treatments for kidney-related ailments.


The phytochemical Isorhamnetin extracted form teh leaves og the Gingko Biloba plant
can be harnessed to treat Kidney Fibrosis

Researchers from Shaanxi University of Chinese Medicine, Xianyang Central Hospital in China, and the University of Yamanashi in Japan collaborated on the study. The team explored how isorhamnetin, which is derived from plants such as Hippophae rhamnoides L. and Ginkgo biloba L., could be harnessed to treat renal fibrosis. Renal fibrosis is known to cause tissue scarring, which eventually leads to kidney failure. The current treatments are limited and often come with serious side effects, creating an urgent need for alternative therapies. The study revealed the remarkable ability of isorhamnetin to induce endogenous hydrogen sulfide (H₂S), offering hope for CKD patients.
 
Key Findings of the Study
The researchers initially hypothesized that isorhamnetin might work by inducing the production of hydrogen sulfide (H₂S), a naturally occurring gas in the body known for its protective and healing properties. Previous research has shown that H₂S can help alleviate liver and lung fibrosis, but its effects on kidney fibrosis were not well understood. The study team created a model using rats with unilateral ureteral obstruction (UUO), a well-known model for studying renal fibrosis. The results were striking.
 
Isorhamnetin not only reduced kidney scarring but also prevented the accumulation of harmful proteins that cause fibrosis. The researchers found that isorhamnetin stimulated the production of enzymes that create H₂S within the body, notably cystathionine lyase (CSE) and cystathionine beta-synthase (CBS). These enzymes play an essential role in generating H₂S, which has been shown to have multiple health benefits, including reducing oxidative stress and inflammation - two key factors in the progression of kidney fibrosis.
 
How Isorhamnetin Works
The primary finding of the study is that isorhamnetin’s protective effects are largely due to its ability to stimulate the production of endogenous H₂S. This increase in H₂S production was shown to reduce oxidative stress in the kidneys, which is a major contributor to the development of fibrosis. The study demonstrated that isorhamnetin targets a specific cellular pathway known as the Keap1-Nrf2 pathway. This pathway is crucial for regulating oxidative stress in the body.
 
Under normal conditions, a protein called Keap1 binds to Nrf2, preventing it from entering the cell nucleus, where it could activate antioxidant genes. Howeve r, isorhamnetin was found to disrupt this interaction by inducing the sulfhydration of Keap1. This modification allowed Nrf2 to move into the nucleus and stimulate the production of antioxidants, reducing the oxidative stress that contributes to kidney damage.
 
Prevention of Epithelial-Mesenchymal Transition (EMT)
Another critical aspect of isorhamnetin’s protective effects is its ability to inhibit the process of epithelial-mesenchymal transition (EMT), which is a key driver of renal fibrosis. EMT is a biological process where epithelial cells, which line the surfaces of organs, transform into mesenchymal cells, which contribute to the formation of fibrotic tissue. This transition plays a significant role in the progression of fibrosis in the kidneys.
 
The study showed that isorhamnetin significantly reduced the expression of proteins involved in EMT, such as alpha-smooth muscle actin (α-SMA) and fibronectin, while promoting the production of E-cadherin, a protein that helps maintain the normal function of epithelial cells. This finding suggests that isorhamnetin not only reduces existing fibrosis but may also help prevent its development in the first place.
 
Liver's Role in H₂S Production
Interestingly, the study revealed that while the kidneys did produce some H₂S in response to isorhamnetin treatment, the liver was the primary source of the increased H₂S levels in the blood. This discovery opens up new avenues for research, as it suggests that treatments aimed at increasing H₂S production in the liver could have widespread benefits for other organs, including the kidneys.

The researchers also conducted experiments on liver cells (HepG2) and found that isorhamnetin increased the production of H₂S in these cells in a dose-dependent manner. The more isorhamnetin the cells were exposed to, the more H₂S they produced, further supporting the idea that isorhamnetin could be used to boost H₂S levels in the body and protect against fibrosis.
 
Potential for Broader Applications
While this study focused on renal fibrosis, the findings suggest that isorhamnetin’s ability to increase H₂S production could have broader applications for other fibrotic diseases. Fibrosis is a common feature of many chronic diseases, including liver cirrhosis, pulmonary fibrosis, and heart disease. Since H₂S has been shown to have protective effects in various organs, isorhamnetin could potentially be used as a treatment for a range of fibrotic conditions.
 
The multifunctional properties of H₂S, including its ability to reduce oxidative stress, inhibit inflammation, and promote tissue repair, make it an attractive target for therapeutic development. Isorhamnetin’s ability to induce H₂S production could pave the way for new treatments that address the underlying causes of fibrosis rather than just managing symptoms.
 
Conclusions
The study highlights the potential of isorhamnetin as a novel treatment for renal fibrosis and possibly other fibrotic conditions. By inducing the production of endogenous H₂S and regulating oxidative stress through the Keap1-Nrf2 pathway, isorhamnetin offers a multifaceted approach to preventing and treating fibrosis.
With further research, isorhamnetin could become a key player in the fight against chronic kidney disease and other fibrosis-related diseases. The ability to target both fibrosis and its underlying causes makes isorhamnetin a promising candidate for future therapies.
 
For CKD patients and those at risk of fibrosis-related diseases, this research offers hope for more effective treatments with fewer side effects. As researchers continue to explore the potential of isorhamnetin, it is clear that this natural compound holds great promise for improving kidney health and beyond.
 
The study findings were published in the peer-reviewed journal: Biomolecules.
https://www.mdpi.com/2218-273X/14/10/1233
 
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