Hepatoprotective effect of crude polysaccharides extracted from Ganoderma lucidum against carbon tetrachloride-induced liver injury in mice

Susilo, Raden Joko Kuncoroningrat; Winarni, Dwi; Husen, Saikhu Akhmad; Hayaza, Suhailah; Punnapayak, Hunsa; Wahyuningsih, Sri Puji Astuti; Sajidah, Elma Sakinatus; Darmanto, Win

doi:10.14202/vetworld.2019.1987-1991

Cited by 20 publications

(13 citation statements)

References 30 publications

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“…Minor histological alterations were observed in the liver, such as diffuse hydropic degeneration in hepatocytes (yellow arrow). The hydropic or vacuolar degeneration could be the result of the disruption of hepatocyte osmoregulatory balance, increasing the intracellular water (Susilo et al 2019). It is worth mentioning that this is a reversible and nonlethal acute injury.…”

Section: Histopathological Analysismentioning

confidence: 99%

Promising self-emulsifying drug delivery system loaded with lycopene from red guava (Psidium guajava L.): in vivo toxicity, biodistribution and cytotoxicity on DU-145 prostate cancer cells

et al. 2021

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Background Self-emulsifying drug delivery systems (SEDDSs) have attracted attention because of their effects on solubility and bioavailability of lipophilic compounds. Herein, a SEDDS loaded with lycopene purified from red guava (nanoLPG) was produced. The nanoemulsion was characterized using dynamic light scattering (DLS), zeta potential measurement, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), lycopene content quantification, radical scavenging activity and colloidal stability in cell culture medium. Then, in vivo toxicity and tissue distribution in orally treated mice and cytotoxicity on human prostate carcinoma cells (DU-145) and human peripheral blood mononuclear cells (PBMC) were evaluated. Results NanoLPG exhibited physicochemical properties with a size around 200 nm, negative zeta-potential, and spherical morphology. The size, polydispersity index, and zeta potential parameters suffered insignificant alterations during the 12 month storage at 5 °C, which were associated with lycopene stability at 5 °C for 10 months. The nanoemulsion showed partial aggregation in cell culture medium at 37 °C after 24 h. NanoLPG at 0.10 mg/mL exhibited radical scavenging activity equivalent to 0.043 ± 0.002 mg Trolox/mL. The in vivo studies did not reveal any significant changes in clinical, behavioral, hematological, biochemical, and histopathological parameters in mice orally treated with nanoLPG at 10 mg/kg for 28 days. In addition, nanoLPG successfully delivered lycopene to the liver, kidney and prostate in mice, improved its cytotoxicity against DU-145 prostate cancer cells—probably by pathway independent on classical necrosis and apoptosis—and did not affect PBMC viability. Conclusions Thus, nanoLPG stands as a promising and biosafe lycopene delivery system for further development of nanotechnology-based health products. Graphical Abstract

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Section: Histopathological Analysismentioning

confidence: 99%

Promising self-emulsifying drug delivery system loaded with lycopene from red guava (Psidium guajava L.): in vivo toxicity, biodistribution and cytotoxicity on DU-145 prostate cancer cells

et al. 2021

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“…In the metabolic process of the body, CCl 4 can generate CCL 3 and CCl 3 O 2 free radicals through the cytochrome P450 enzymes, which may cause a structural collapse of liver cell membranes and enhance their permeability, and large amounts of intracellular enzymes, including ALT, AST, and ALP are released into the bloodstream, resulting in liver damage (Guo et al, 2016;Susilo et al, 2019). Consequently, the measurement of serum ALT, AST, and ALP activity is an essential criterion for assessing ALI (Xie et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of hydroxysafflor yellow A on acute liver injury based on transcriptomics

Hou

Zhang

et al. 2022

Front. Pharmacol.

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Objective: To investigate how Hydroxysafflor yellow A (HSYA) effects acute liver injury (ALI) and what transcriptional regulatory mechanisms it may employ.Methods: Rats were randomly divided into five groups (n = 10): Control, Model, HSYA-L, HSYA-M, and HSYA-H. In the control and model groups, rats were intraperitoneally injected with equivalent normal saline, while in the HSYA groups, they were also injected with different amounts of HSYA (10, 20, and 40 mg/kg/day) once daily for eight consecutive days. One hour following the last injection, the control group was injected into the abdominal cavity with 0.1 ml/100 g of peanut oil, and the other four groups got the same amount of a peanut oil solution containing 50% CCl4. Liver indexes were detected in rats after dissection, and hematoxylin and eosin (HE) dyeing was utilized to determine HSYA’s impact on the liver of model rats. In addition, with RNA-Sequencing (RNA-Seq) technology and quantitative real-time PCR (qRT-PCR), differentially expressed genes (DEGs) were discovered and validated. Furthermore, we detected the contents of anti-superoxide anion (anti-O2−) and hydrogen peroxide (H2O2), and verified three inflammatory genes (Icam1, Bcl2a1, and Ptgs2) in the NF-kB pathway by qRT-PCR.Results: Relative to the control and HSYA groups, in the model group, we found 1111 DEGs that were up-/down-regulated, six of these genes were verified by qRT-PCR, including Tymp, Fabp7, Serpina3c, Gpnmb, Il1r1, and Creld2, indicated that these genes were obviously involved in the regulation of HSYA in ALI model. Membrane rafts, membrane microdomains, inflammatory response, regulation of cytokine production, monooxygenase activity, and iron ion binding were significantly enriched in GO analysis. KEGG analysis revealed that DEGs were primarily enriched for PPAR, retinol metabolism, NF-kB signaling pathways, etc. Last but not least, compared with the control group, the anti-O2− content was substantially decreased, the H2O2 content and inflammatory genes (Icam1, Bcl2a1, and Ptgs2) levels were considerably elevated in the model group. Compared with the model group, the anti-O2− content was substantially increased, the H2O2 content and inflammatory genes (Icam1, Bcl2a1, and Ptgs2) levels were substantially decreased in the HSYA group (p < 0.05).Conclusion: HSYA could improve liver function, inhibit oxidative stress and inflammation, and improve the degree of liver tissue damage. The RNA-Seq results further verified that HSYA has the typical characteristics of numerous targets and multiple pathway. Protecting the liver from damage by regulating the expression of Tymp, Fabp7, Serpina3c, Gpnmb, Il1r1, Creld2, and the PPAR, retinol metabolism, NF-kappa B signaling pathways.

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“…The extraction procedure was performed according to Susilo et al . [ 19 ]. Briefly, 500 g of pounded G. applanatum was heated in 10 L of distilled water at 75°C for 6 h with occasional stirring, and the extract was filtered using Whatman filter paper (Merck, Darmstadt, Germany).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2022

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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.

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Hepatoprotective effect of crude polysaccharides extracted from Ganoderma lucidum against carbon tetrachloride-induced liver injury in mice

Cited by 20 publications

References 30 publications

Promising self-emulsifying drug delivery system loaded with lycopene from red guava (Psidium guajava L.): in vivo toxicity, biodistribution and cytotoxicity on DU-145 prostate cancer cells

Promising self-emulsifying drug delivery system loaded with lycopene from red guava (Psidium guajava L.): in vivo toxicity, biodistribution and cytotoxicity on DU-145 prostate cancer cells

Mechanism of hydroxysafflor yellow A on acute liver injury based on transcriptomics

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

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