Research Update | Professor Yang Baoxue’s team from Peking University confirms that ganoderic acid A is the primary component of ganoderic triterpenes responsible for kidney protection in Ganoderma lucidum.

The team led by Professor Yang Baoxue, Director of the Department of Pharmacology at the School of Basic Medical Sciences of Peking University, has successively published two papers in "Acta Pharmacologica Sinica" (Chinese Journal of Pharmacology) at the end of 2019 and the beginning of 2020, confirming that Ganoderma lucidum exerts a delaying effect on renal fibrosis and polycystic kidney disease. The primary active ingredient responsible for these effects is ganoderic acid A.

Ganoderic acid A slows the progression of renal fibrosis.

Researchers surgically ligated the unilateral ureter of mice. Fourteen days later, the mice exhibited renal tubular damage and renal fibrosis due to impaired urine excretion. At the same time, serum levels of blood urea nitrogen (BUN) and creatinine (Cr) also increased, indicating impaired renal function.

However, if ganoderic acid is administered via intraperitoneal injection at a daily dose of 50 mg/kg immediately after unilateral ureteral ligation in mice, then 14 days later, the degree of renal tubular injury, renal fibrosis, and renal functional impairment will all be significantly milder compared to that in mice without ganoderic acid protection.

The ganoderic acids used in the experiment are a mixture containing at least a dozen different ganoderic acids, with ganoderic acid A (16.1%), ganoderic acid B (10.6%), and ganoderic acid C2 (5.4%) being the most abundant.

In vitro cell experiments have shown that ganoderic acid A (100 μg/mL) exhibits the best inhibitory effect on renal fibrosis among the three compounds tested—indeed, it is even more effective than the original ganoderic acid mixture—and does not exert any cytotoxic effects on renal cells. Therefore, the researchers conclude that ganoderic acid A is likely the primary active component responsible for Ganoderma’s ability to delay renal fibrosis.

Ganoderic Acid A Slows the Progression of Polycystic Kidney Disease

Unlike renal fibrosis, which is often caused by external factors, polycystic kidney disease (hereafter referred to as PKD) is triggered by a genetic mutation on a specific chromosome. Ninety percent of cases are hereditary. Typically, the disease manifests around the age of 40. Over time, cysts in both kidneys gradually enlarge and multiply, eventually compressing and damaging normal kidney tissue, thereby impairing kidney function.

Faced with this irreversible disease, slowing down the deterioration of kidney function has become the primary therapeutic goal. As early as the end of 2017, Professor Yang Baoxue’s team published a report in the medical journal Kidney International confirming that ganoderma triterpenes can delay the onset and alleviate the severity of polycystic kidney disease.

However, there are numerous types of ganoderic triterpenes in Lingzhi mushrooms—so which one exactly plays a crucial role? To find out, they isolated and tested each of the following ganoderic triterpenes one by one: ganoderic acids A, B, C2, D, F, G, T, and DM, as well as ganoderenic acids A, B, D, and F.

In vitro experiments showed that none of these 12 triterpenoid compounds affected the viability of renal cells, and their safety levels were nearly identical. However, there were significant differences in their ability to inhibit the growth of renal cysts, with ganoderic acid A demonstrating the best efficacy.

Animal experiments have also shown that when mice born with polycystic kidney disease were subcutaneously injected with 50 mg/kg of ganoderic acid A daily for four days, compared to polycystic kidney disease mice not protected by ganoderic acid A, renal enlargement was better controlled, the renal cysts were smaller, and the area occupied by renal cysts was reduced by approximately 40%.

The effective dose of ganoderic acid A in animals is only one-quarter of the dose used in the same experiment with total triterpenes, indicating that ganoderic acid A is indeed the primary active component responsible for the triterpenes from Ganoderma lucidum in slowing the progression of polycystic kidney disease.

Meanwhile, injecting the same dose of ganoderic acid A does not affect the kidney size of genetically normal mice, indicating that ganoderic acid A possesses a certain degree of safety.

Reishi mushrooms containing ganoderic acid A offer even more remarkable kidney-protecting effects.

From renal fibrosis to kidney failure, one could say that chronic kidney disease caused by various different etiologies—such as diabetes—is inevitably destined to follow an irreversible path.

For patients with polycystic kidney disease, the rate of renal function decline may be faster—according to statistics, about half of all PKD patients will progress to kidney failure around the age of 60 and will then require lifelong dialysis.

Whether due to acquired or congenital factors, reversing kidney disease is no easy feat! But if we can slow down the progression of the disease—to a pace that balances with the length of one’s life—perhaps we can give those living with the illness less of a sense of fate and more of a rich, colorful experience.

Professor Yang Baoxue’s team has already demonstrated through cell and animal experiments that ganoderic acid A, the most abundant triterpene in Ganoderma lucidum, is the key bioactive component responsible for Ganoderma’s kidney-protecting effects.

These research findings highlight just how rigorous the scientific study of Lingzhi is—allowing us to pinpoint exactly which components are responsible for its efficacy, rather than relying on mere speculation.

Of course, it’s not to say that only ganoderic acid A in reishi mushroom can protect the kidneys—other components certainly play a role as well.

For example, another paper published by Professor Yang Baoxue—also on the theme of kidney protection—points out that Ganoderma lucidum polysaccharide extract can reduce oxidative damage to kidney tissue by exerting an antioxidant effect.

The “total triterpenes from Ganoderma,” which include a variety of triterpenoid compounds such as ganoderic acids, ganoderenic acids, and ganoderol, work synergistically to delay renal fibrosis and the progression of polycystic kidney disease—effects that cannot be overlooked.

Moreover, addressing kidney health isn't solely about focusing on kidney protection itself. Other factors—such as regulating the immune system, improving the “three highs,” balancing endocrine function, calming the mind, and promoting better sleep—will undoubtedly also contribute to kidney health. And these benefits cannot be fully achieved by lingzhi acid A alone.

The value of Lingzhi lies precisely in its diverse composition and multifaceted effects, which can work synergistically to help the body find its optimal balance. However, when it comes to kidney health, if Lingzhi acid A is missing, it’s just like a basketball team lacking a key player—its overall strength would be significantly diminished.

Reishi mushroom containing ganoderic acid A

Even more remarkable kidney-protecting effects

Even more worth looking forward to for you and me.

[References]

1. Geng XQ, et al. Ganoderic acid inhibits renal fibrosis by suppressing the TGF-β/Smad and MAPK signaling pathways. Acta Pharmacol Sin. 2019 Dec 5. doi: 10.1038/s41401-019-0324-7.

2. Meng J, et al. Ganoderic acid A is the active ingredient of Ganoderma triterpenes that inhibits the development of renal cysts in polycystic kidney disease. Acta Pharmacol Sin. 2020 Jan 7. doi: 10.1038/s41401-019-0329-2.

3. Su L, et al. Ganoderma triterpenes retard renal cyst development by downregulating Ras/MAPK signaling and promoting cell differentiation. Kidney Int. 2017 Dec; 92(6):1404-1418. doi: 10.1016/j.kint.2017.04.013.

4. Zhong D, et al. Ganoderma lucidum polysaccharide peptide prevents renal ischemia-reperfusion injury by counteracting oxidative stress. Sci Rep. 2015 Nov 25; 5:16910. doi: 10.1038/srep16910.

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