Effect of crude Ganoderma applanatum polysaccharides as a renoprotective agent against carbon tetrachloride-induced early kidney fibrosis in mice

Abstract

Background and Aim: Interstitial fibrosis is the final stage of chronic kidney injury, which begins with an inflammatory process. Crude Ganoderma applanatum polysaccharides are known to have anti-inflammatory properties. The potential role of crude G. applanatum polysaccharides in renal fibrosis through pro-inflammatory cytokines needs further investigation. This study aimed to determine the renoprotective effect of crude G. applanatum polysaccharide extract in mice with carbon tetrachloride (CCL4)-induced early kidney fibrosis. Materials and Methods: This study was conducted for 4 weeks using 24 male BALB/c mice selected for their metabolic stability. The mice were randomly divided into six groups, including control (CG), model (MG), silymarin group and crude G. applanatum polysaccharide extract groups comprising doses of 25, 50, and 100 mg/kg body weight. After sacrificing the mice, whole blood was analyzed for urea and creatine levels, and kidney tissue was prepared to assess tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), hyaluronic acid (HA), and laminin levels, both using enzyme-linked immunosorbent assay. Kidney histology was determined using hematoxylin and eosin staining, while the extracellular matrix (ECM) components were stained using Masson's trichome staining. The α-smooth muscle actin (α-SMA) concentration was determined using immunohistochemistry. These parameters were measured to determine the effectiveness of the crude G. applanatum polysaccharide extract in preventing interstitial fibrosis. Results: Administration of crude G. applanatum polysaccharides effectively prevented increases in kidney weight and physiological enzymes, pro-inflammatory cytokines, and ECM production compared with those in the MG, as evidenced by the low levels of urea, creatinine, TNF-α, IL-6, HA, and laminin. Histopathological results also showed that crude G. applanatum polysaccharides prevented the occurrence of inflammatory infiltration, desquamated nuclei, cytoplasm debris, rupture at the brush border, dilatation of the glomeruli space and lumen of the proximal tubule, and necrotic cells compared with the MG. Masson's trichrome staining revealed lower collagen levels in the interstitial tubules of kidney tissue than those in the MG. Immunohistochemical analysis revealed low α-SMA expression in the crude G. applanatum polysaccharides treatment groups than that in the MG. Conclusion: The crude polysaccharide extract of G. applanatum has a protective effect that prevents the progression of kidney fibrosis in mice.

The Effect of G. applanatum Crude Polysaccharide Extract on Proinflammatory Cytokines and Proapoptotic Caspases in HeLa Cell Line: An In Vitro Study

“…G. applanatum specimens were sourced from Tulungagung, East Java, Indonesia. The extraction procedure, as detailed by Susilo et al [ 14 ], was pursued. Dr. Ni'matuzzahroh conducted the identification based on a designated key book [ 19 ].…”

“…While early-stage cervical cancer may remain asymptomatic, advanced stages manifest symptoms such as vaginal bleeding, ureteral obstruction, hydronephrosis, uremia, and pericarditis [8][9][10][11]. Te signifcance of proinfammatory cytokines lies in their role as stimulators in phosphorylating the inhibitor of κB (IKK) complex, a pivotal step in translocating NF-κB to the nucleus [12][13][14][15][16]. Subsequently, NF-κB engages in transcription, yielding proinfammatory cytokines that foster cancer cell survival.…”

Potential Protective Effects of Ethanolic Extract of Butterfly Pea (Clitoria ternatea Linn) Flower Against Carbon Tetrachloride-Induced Hepatotoxicity Rats

“…Furthermore, a dosedependent relationship was observed in the rate of decrease for each of these parameters. According to several researchers (Elhassanneen et al,2012 andSusilo et al,2019), CCl4 -induced liver injury is regularly employed to investigate the hepatoprotective effects of pharmaceuticals and natural substances. CCl4 is metabolized by liver cytochrome P450 into trichloromethyl (CCl3-) radicals, which then combine with O2 to create trichloromethyl peroxyl (CCl3OO-) radicals, leading to liver damage.…”

The modulation effects of plant‐derived bioactive ingredients on chronic kidney disease: Focus on the gut–kidney axis

“…Administration of polysaccharides from Chinese chives in 200 mg of body weight could significantly reverse serious renal pathological damage by 59.2% in adenine‐induced CRF mice through antioxidant, anti‐inflammatory, and antifibrotic activities (Q. Li et al., 2018). The renoprotective effect of crude Ganoderma applanatum polysaccharide (100 mg/kg of body weight) is evidenced by the decrease in proinflammatory cytokines, urea, creatinine, and positive histopathological results (Susilo et al., 2022). Polysaccharides extracted from Cordyceps cicadae exerted a beneficial effect on tubulointerstitial fibrosis in diabetic nephropathy rats by suppressing inflammatory response, modulating gut microbiota dysbiosis, and blocking the TLR4/NF‐κB and TGF‐β1/Smad pathways (J. Yang et al., 2020).…”

“…Li et al, 2018). The renoprotective effect of crude Ganoderma applanatum polysaccharide (100 mg/kg of body weight) is evidenced by the decrease in proinflammatory cytokines, urea, creatinine, and positive histopathological results (Susilo et al, 2022). Polysaccharides extracted from Cordyceps cicadae exerted a beneficial effect on tubulointerstitial fibrosis in diabetic nephropathy rats by suppressing inflammatory response, modulating gut microbiota dysbiosis, and blocking the TLR4/NF-κB and TGF-β1/Smad pathways (J. .…”