A new study published March 4, 2022, has validated more local plants for the prevention and treatment of kidney diseases. Top on the list is ginger, grape, turmeric, beetroot juice
A new study published March 4, 2022, has validated more local plants for the prevention and treatment of kidney diseases. Top on the list is ginger, grape, turmeric, beetroot juice, stinging nettle, onions, apples, tea, papaya, bitter leaf, and guava leaves.
Chronic kidney disease (CKD) is debilitating, increasing in incidence worldwide, and a financial and social burden on health systems. Kidney failure, the final stage of CKD, is life-threatening if untreated with kidney replacement therapies. Current therapies using commercially-available drugs, such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and calcium channel blockers, generally only delay the progression of CKD.
Herbal Supplements And Kidney Disease
Plants, algae and fungi have been utilised as natural medicines throughout human history. Medicinal plants are regarded as an acceptable, cheap, easily available and relatively safe source of many active compounds for pharmaceuticals. In China, the use of traditional herbal medicine for kidney disease has shown some advantages over single conventional drug treatment. The beneficial effect of medicinal plants on kidney disease is often derived from their ability to boost the natural antioxidant defence mechanisms in the body. Different types of phytochemicals such as flavonoids, vitamins, resveratrol, anthocyanin, curcumin and phenolic acid are often found in plant-based medicines and may act as antioxidants.
The researchers have identified and validated plants known to be beneficial in CKD and to have minimal adverse outcomes. They said although, by no means restricted to these plants, the benefit has been demonstrated from Rheum spp. (Rhubarb), Astragalus membranaceous (Astragalus), Cordyceps Sinensis (CS), Triptirygium wildfordii (TwHF), Abelmoschus manihot (L.) medic (AM), Salvia miltiorrhiza (SM), Vitis vinifera (Grape), and Zingiber officinale (Ginger). These plants and their extracts are sometimes used alone, but in many countries, they are used in polyherbal for the treatment of kidney disease.
Ginger is used widely as a spice but also often in folk medicine. It belongs to the Zingiberaceae family and has been cultivated for thousands of years, especially in China and South Asian countries. Ginger contains many beneficial compounds, the most important of which are 6-, 8-, and 10-gingerol and 6-shogaol. It displays diverse beneficial biological actions due to its potent antioxidant, anti-inflammatory, anti-tumour, anti-diabetic and neuroprotective activities.
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In pre-clinical animal models of kidney and cardiovascular diseases, ginger extracts lowered blood glucose levels, restored the total carbohydrates, pyruvate, glycogen and total protein in kidney tissue, promoted the regeneration of tubules and restored glomeruli, and reduced fatty infiltration. One clinical trial of ginger extract in CKD patients on peritoneal dialysis demonstrated that daily administration of 1000 mg ginger reduced serum fasting glucose, a risk factor for diabetes, diabetic nephropathy and cardiovascular disease. There have been no adverse side effects reported when doses are kept to a moderate level.
There are many other plants reported to have benefits for kidney failure and/or CKD. Rutin (or quercetin) is a flavonoid present in onions, apples, tea and red wine.
This plant extract is readily available “over the counter” and has demonstrated strong antioxidant and anti-inflammatory properties in the heart and liver in a high fat-high carbohydrate diet model of metabolic syndrome in rats.
Evidence Based Herbal Medicine
Rutin also protected the kidney against ischemia-reperfusion injury, cisplatin-induced nephrotoxicity, and diabetic nephropathy. It normalized BUN, thereby modulating a key factor in the pathogenesis of CKD. However, some other studies did not show benefits.
For example, rutin may induce protein-energy malnutrition in CKD. Although there are some promising results, more analyzes are needed to confirm whether, or not, preclinical and clinical benefits exist for this plant extract, particularly in the context of CKD.
Clinically, Glycyrrhiza glabra extracts consistently decreased pre-dialysis serum potassium concentrations in chronic hemodialysis patients. Silybum marianum, known as “milk thistle” or silymarin, is a very safe herb that protects against kidney failure and end-stage diabetic nephropathy. Significant benefits have been claimed for Lespedeza tincture for both AKI and CKD patients.
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Clinically, beetroot juice decreased peripheral systolic and diastolic blood pressure, mean arterial pressure, improved kidney function, histological damage and kidney prognosis, and prevented cardiovascular events.
In a recent study, a beetroot protease inhibitor was isolated and characterized. The results showed the potential of such plant protease inhibitors for peptide-based drug discovery against targets involved in diseases such as cancers and immune system-related diseases, such as is seen in CKD in some instances. Coptis rhizome extracts significantly reduced biomarkers of kidney damage, such as urinary albumin-to-creatine ratio, urinary osteopontin and KIM-1, and improved kidney hemodynamics. In addition, clinically, it decreased inflammation and oxidative stress.
Extracts of Urtica dioica, or “stinging nettle”, significantly attenuated kidney damage and tubular atrophy, loss of brush border, hydropic epithelial cell degeneration, glomerular shrinkage, and tubulointerstitial fibrosis, as well as demonstrating clinical benefits in patients undergoing partial nephrectomy or kidney transplantation. The polyherbal named “Sairei-To” significantly decreased urinary protein excretion, hematuria and normalized proteinuria in CKD patients.
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A dietary supplementation with curcumin (turmeric) reduced oxidative stress and proteinuria in CKD patients. A combination of Curcuma longa and Boswellia serrata decreased the levels of inflammatory cytokines and ameliorated inflammatory markers in patients with CKD.
Rhubarb, derived from the root of Rheum spp indigenous to Asia, belongs to the Polygonaceae family. Some species are cultivated for their potential to treat CKD. Rhubarb contains compounds such as saponins, flavonoids, volatile oils, polysaccharides, tannins, stilbene glycosides (resveratrol and piceatannol) and anthraquinone glycosides (physcion, aloe-emodin, chrysophanol, emodin and rhein). The anthraquinone glycosides may have some inherent toxicities, but they can be removed from extracts to produce an effective extract that is nephroprotective. Many clinical and pre-clinical trials have consistently shown that extracts of rhubarb can reduce serum creatinine levels and offset other metabolic dysfunction related to kidney failure.
In CKD therapy, rhubarb increases the excretion of nitrogenous and other waste products through the intestine and ameliorates uremic toxin accumulation, as demonstrated in various pre-clinical animal models of kidney failure. Using a model of diabetic nephropathy in mice, the proposed mechanism was thought to target the gut-kidney axis and trigger protective gut microbiota, rather than being directly nephroprotective.
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The two primary active anthraquinones in rhubarb are rhein and emodin. Rhein prevents kidney damage by modulating various signalling pathways. It down-regulates the Wnt/β-catenin signalling pathway, up-regulates Sirtuin 1, decreases EMT that normally leads to fibrosis and ameliorates dyslipidemia. Rhein also improves cell metabolism through modulation of the glucose transporter I, decreasing mesangial cell hypertrophy and glomerulosclerosis.
Emodin reduces glycation of proteins, inhibits the lipopolysaccharide-induced expression of TLR4 and down-regulates pro-inflammatory TNF-α and IL-6 in the damaged kidney. Emodin also decreases mesangial cell proliferation by inhibiting cellular FLICE-like inhibitor protein, TGF-β1 and fibronectin, p38 MAPK, differentiation and maturation of dendritic cells, and increases the number of regulatory T cells.
These results indicate that the active ingredients in rhubarb have multiple mechanisms of action for the treatment of CKD, including regulation of inflammation and the immune response. Most of these reports have used pre-clinical models. Clinically, rhubarb extract alone, or as a polyherbal, was beneficial in CKD patients, delaying CKD progression and decreasing adverse effects of hemodialysis. The most common adverse side effects of rhubarb are nausea, vomiting, diarrhoea, electrolyte disorders and liver toxicity.
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Astragalus membranaceus (synonymous name of Astragalus propinquus), belongs to the family Fabaceae and the genus Astragalus, which has more than 3000 species worldwide. The plant is indigenous to the north and eastern regions of China but is grown worldwide and used widely in complementary and alternative medicines. Astragalus contains more than 60 bioactive compounds, including polysaccharides, saponins (astragalosides I–VII), flavonoids, amino acids and trace elements. In vitro and in vivo pre-clinical trials have revealed that Astragalus extract has potent antioxidant and anti-inflammatory effects. Other mechanisms include downregulating angiotensin receptors, inhibiting nitric oxide synthase and TNF-α production, and stimulating vascular endothelial growth factors and the immune system. In addition, the plant extracts from Astragalus can rebalance profibrotic TGF-β/Smad signalling activity and inhibit endoplasmic reticulum stress-induced pathways.
Several pre-clinical CKD models reported that the plant extract, either alone or as a polyherbal, showed anti-fibrotic effects, ameliorated proteinuria, attenuated kidney injury and promoted Renoprotective effects. Wojcikowski et al. performed a pre-clinical trial in rats using the unilateral ureteral obstruction (UUO) model of kidney fibrosis, with or without Astragalus membranaceus and Angelica sinensis (A and A). The ACEi Enalapril was administered in drinking water in some groups. The combined effect of A and A, with or without Enalapril, had anti-fibrotic benefits. Several clinical trials have reported that Astragalus significantly ameliorated CKD by decreasing proteinuria, with a corresponding increase in creatinine clearance, and haemoglobin levels. Astragalus is safe for most of recipients.
However, the plant is known to inhibit CYP3A4 hence it could affect the action of some other drugs that are metabolized by this enzyme.
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CS is a fungus that derives its nutrients from the larvae of Lepidoptera. It is endemic to the Tibetan plateau but is produced commercially now. Various bioactive compounds, including amino acids, polysaccharides, organic acids, trace elements, nucleosides, peptides, steroids and other chemical components are present in CS extracts. The ability of CS to ameliorate urinary disorders and edema was described over 2000 years ago in
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