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Cisplatin, a proven effective chemotherapeutic agent, has been used clinically to treat malignant solid tumors, whereas its clinical use is limited by serious side effect including nephrotoxicity. Platycodin D (PD), the major and marked saponin isolated from Platycodon grandiflorum, possesses many pharmacological effects. In this study, we evaluated its protective effect against cisplatin-induced human embryonic kidney 293 (HEK-293) cells injury and elucidated the related mechanisms. Our results showed that PD (0.25, 0.5, and 1 μM) can dose-dependently alleviate oxidative stress by decreasing malondialdehyde and reactive oxygen species, while increasing the levels of glutathione, superoxide dismutase, and catalase. Moreover, the elevation of apoptosis including Bax, Bad, cleaved caspase-3,-9, and decreased protein levels of Bcl-2, Bcl-XL induced by cisplatin were reversed after PD treatment. Importantly, PD pretreatment can also regulate PI3K/Akt and ERK/JNK/p38 signaling pathways. Furthermore, PD was found to reduce NF-κB-mediated inflammatory relative proteins. Our finding indicated that PD exerted significant effects on cisplatin induced oxidative stress, apoptosis and inflammatory, which will provide evidence for the development of PD to attenuate cisplatin-induced nephrotoxicity., (© 2020 Wiley Periodicals LLC.)

Although ginseng ( Panax ginseng C.A. Meyer) has received extensive attention in the treatment and prevention of type 2 diabetes mellitus (T2DM) in the past few decades, there are few studies on the complications of T2DM. At present, obesity-linked diabetic nephropathy (DN) has become the most prevailing element of the end-stage renal failure in the world. The aim of this work is to evaluate the ameliorative effects of ginsenoside Rh1 (G-Rh1) on DN induced by high fat diet plus streptozotocin (HFD/STZ) through some potential and combined mechanisms of action. The results showed that G-Rh1 treatment at 5 and 10 mg/kg for 8 weeks exerted excellent effects in controlling fasting blood glucose (FBG), improving glucose tolerance, and increasing insulin level. In addition, G-Rh1 effectively prevents the excessive production of advanced glycation end products (AGEs), a diabetic nephropathy marker, in HFD/STZ induced DN mice. Meanwhile, oxidation indicators including SOD, GSH, and MDA were improved by G-Rh1 treatment to varying degrees. It is worth noting that G-Rh1 not only inhibits the secretion of Nox1 and Nox4 in kidney tissues, but also has an inhibitory effect on inflammatory factors and NF-[Formula: see text]B signaling pathway. Importantly, further in-depth research on molecular mechanisms provides vital evidence that the ameliorative effect of G-Rh1 on DN is related to the inhibition of apoptosis and the AMPK/PI3K/Akt signaling pathway. In summary, G-Rh1 may be of great value in improving the treatment of DN although more experimental data is needed.

Heat stress (HS) reaction is a stress response caused by adverse conditions. Currently, the incidence of reproductive malignancies particularly in males has been constantly increasing. This work investigated the effects of saponins derived from the stems and leaves of Panax ginseng (GSLS) on testicular injury induced by scrotal hyperthermia in mice. GSLS (150, 300 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43°C for 18 min on seventh day. HS induced a significant loss of multinucleate giant cells, desquamation of germ cells in destructive seminiferous tubules. Moreover, HS reduced the serum testosterone, testicular tissue superoxide dismutase activity and glutathione (GSH) content, while significantly enhanced the production of malondialdehyde (p < .05). GSLS exhibited the protective potential against HS-induced injury not only by modulating Bcl-2 family and caspase protease family, but also by suppressing the protein levels of heme oxygenase-1 (HO-1), heat shock protein 70 (HSP70), hypoxia inducible factor-1α (HIF-1α) and activation of Mitogen-activated protein kinase (MAPK) signaling pathways (p < .05). In conclusion, we clearly demonstrated that GSLS exhibited a significant protective effect against HS-induced testicular dysfunction, mainly the inhibition of oxidative stress associated apoptosis partly via regulation of the MAPK signaling pathway., (© 2020 John Wiley & Sons Ltd.)

Although growing evidence has shown that ginseng (Panax ginseng C.A. Meyer.) exerts strong protective and preventive effects on cisplatin-induced side effects, including nephrotoxicity, ototoxicity and cardiotoxicity, the ameliorative effects of ginseng on intestinal damage caused by cisplatin are unknown to date. Red ginseng (RG), a major processed product of the roots of Panax ginseng C.A. Meyer, can be used to control chemotherapy drug-induced multiple toxicity. In the present work, an animal model of cisplatin-induced intestinal injury was established to evaluate the ameliorative effects of RG and their underlying molecular mechanism for the first time. The results showed that a single cisplatin injection (20 mg kg -1 ) leads to loss of body weight, shrinkage of the small intestine, and sharp increase of the intestinal function index of diamine oxidase (DAO). These symptoms were remarkably relieved after the administration of RG at 300 and 600 mg kg -1 for 10 continuous days, respectively. In addition, RG markedly reduced the increase in malondialdehyde (MDA) levels and the consumption of superoxide dismutase (SOD) and catalase (CAT) caused by cisplatin-induced oxidative stress. Furthermore, RG pretreatment dramatically improved the cisplatin-induced apoptosis of intestinal villous cells, irregular nuclear arrangement, ablation of crypt cells, and damage to the mechanical barrier. In this study, pharmacological methods have been used to prove that RG can inhibit cisplatin intestinal toxicity by activating the PI3K/AKT signaling pathway to inhibit apoptosis and by antagonizing the MAPK-mediated autophagy pathway.

Oxidative stress is considered as a major factor in aging and exacerbates aging process through a variety of molecular mechanisms. D-galactose, a normal reducing sugar with high dose can cause the accumulation of reactive oxygen species (ROS) or stimulate free radical production indirectly by the formation of advanced glycation end products in tissues, finally resulting in oxidative stress. 20(R)-ginsenoside Rg3 (20(R)-Rg3), a major and representative component isolated from red ginseng ( Panax ginseng C.A Meyer), has been shown to observably have an anti-oxidative effect. We thereby investigated the beneficial effects of 20(R)-Rg3 on D-galactose-induced oxidative stress injury and its underlying mechanisms. Our results showed that continuous injection of D-galactose with 800[Formula: see text]mg/kg/day for 8 weeks increased the levels of alanine aminotransferase (ALT) and blood urea nitrogen (BUN). However, such increases were attenuated by the treatment of 20(R)-Rg3 for 4 weeks. Meanwhile, 20(R)-Rg3 markedly inhibited D-galactose-caused oxidative stress in liver and kidney. The anti-oxidants, including catalase (CAT) and superoxide dismutase (SOD), were elevated in the mice from 20(R)-Rg3-treated group compared with that from D-galactose group. In contrast, a significant decrease in levels of cytochrome P450 E1 (CYP2E1) and the lipid peroxidation product malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) were observed in the 20(R)-Rg3-treated group. These effects were associated with a significant increase of AGEs. More importantly, 20(R)-Rg3 effectively attenuated D-galactose induced apoptosis in liver and kidney via restoring the upstream PI3K/AKT signaling pathway. Taken together, our study suggests that 20(R)-Rg3 may be a novel and promising anti-oxidative therapeutic agent to prevent aging-related injuries in liver and kidney.

Objectives: Based on previous reports that ginsenosides have been shown to exert better preventive effects on cisplatin-induced kidney injury, the present work aims to evaluate the protective effects of ginsenoside Rb3 (G-Rb3) on cisplatin-induced renal damage and underlying mechanisms in vivo and in vitro., Materials and Methods: The protective effect of G-Rb3 on cisplatin-induced acute renal failure in ICR mouse model and HEK293 cell model was investigated, and the underlying possible mechanisms were also explored. For animal experiment, renal function, kidney histology, inflammation, oxidative stress, relative protein molecules involved in apoptosis and autophagy signalling pathways were assessed. In addition, rapamycin (a specific inhibitor of mTOR), compound C (a specific inhibitor of AMPK) and acetylcysteine (NAC, a specific ROS scavenger) were employed to testify the effects of AMPK/mTOR signal pathway on the protective effects of G-Rb3 in HEK293 cells., Results: Pre-treatment with G-Rb3 at doses of 10 and 20 mg/kg for ten days significantly reversed the increases in serum creatinine (CRE), blood urea nitrogen (BUN) and malondialdehyde (MDA), and decrease in glutathione (GSH) content and superoxide dismutase (SOD) activity. Histopathological examination further revealed that G-Rb3 inhibited cisplatin-induced nephrotoxicity. G-Rb3 diminished cisplatin-induced increase in protein expression levels of p62, Atg3, Atg5 and Atg7, and decrease in protein expression level of p-mTOR and the ratio of LC3-I/LC3-II, indicating that G-Rb3 suppressed cisplatin-induced activation of autophagy. Inhibition of autophagy induced inactivation of apoptosis, which suggested that autophagy played an adverse effect on cisplatin-evoked renal damage. Further, we found that G-Rb3 might potentially modulate the expressions of AMPK-related signal pathways., Conclusions: These findings clearly suggested that G-Rb3-mediated alleviation of cisplatin-induced nephrotoxicity was in part due to regulation of AMPK-/mTOR-mediated autophagy and inhibition of apoptosis in vitro and in vivo., (© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Platycodin D (PD), a major saponin derived and isolated from the roots of Platycodon grandiflorum, exerts potent growth inhibition and strong cytotoxicity against various cancer cell lines. However, the anti-tumor efficacy of PD on H22 hepatocellular carcinoma remains unknown. In the present study, we aimed to explore the anti-hepatoma activity in vivo and the underlying mechanism of PD in H22 tumor-bearing mice. The results revealed that PD could considerably suppress tumor growth with no significant side effects on immune organs and body weight. Further investigations showed that the levels of serum cytokines, including interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-2 (IL-2), were enhanced by PD administration. On the other hand, PD inhibited the production of vascular endothelial growth factor (VEGF) in serum of H22 tumor mice. Additionally, the observations from H&E and Hoechst 33258 staining results demonstrated that PD noticeably induced apoptosis in H22 hepatocellular carcinoma cells. Importantly, immunohistochemical analysis showed that PD treatment increased Bax expression and decreased Bcl-2 and VEGF expression of H22 tumor tissues in a dose-dependent manner. Taken together, the findings in the present investigation clearly demonstrated that the PD markedly suppressed the tumor growth of H22 transplanted tumor in vivo at least partly via improving the immune functions, inducing apoptosis, and inhibiting angiogenesis.

Aim: To explore the role of focal adhesion kinase (FAK) in the apoptosis in culture-activated rat hepatic stellate cells (HSCs) using a specific anti-FAK antibody., Methods: Rat HSCs were prepared from Wistar rats by in situ perfusion of collagenase and pronase and single-step density Nycodenze gradient. Culture-activated HSCs were serum-starved and treated with the anti-FAK antibodies for 24, 48 or 72 h. The apoptosis of HSC was detected by DNA-fragment assay, flow cytometry and caspase-3 activity determination. The expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA was assessed by reverse transcription polymerase chain reaction (RT-PCR)., Results: The experiment showed that anti-FAK antibodies induced apoptosis of culture-activated rat HSCs. This phenomenon displayed the classical features of apoptotic cell death (DNA fragmentation, cell cycle analysis) after treated with 30 mg.L(-1) FAK antibody for 72 h, and accompanied by a significant increase of caspase-3 activity(1208+/-76) vs (309+/-28) nmol.min(-1).g(-1), t=208.5, P<0.05. Meanwhile, treatment with the FAK antibody in HSCs could markedly decrease the TIMP-1 mRNA expression (0.07+/-0.01 vs 0.38+/-0.03, t=2.72, P<0.05)., Conclusion: FAK plays an important role in the survival of HSCs and the specific anti-FAK antibody could induce the apoptosis in rat HSCs.

Saponins from the roots of Platycodon grandiflorum, an edible medicinal plant, have shown a wide range of beneficial effects on various biological processes. In this study, an animal model was established by a single intraperitoneal injection of cisplatin (20 mg/kg) for evaluating the protective effects of saponins from the roots of P. grandiflorum (PGS, 15 mg/kg and 30 mg/kg) in mice. The results indicated that PGS treatment for 10 days restored the destroyed intestinal mucosal oxidative system, and the loosened junctions of small intestinal villi was significantly improved. In addition, a significant mitigation of apoptotic effects deteriorated by cisplatin exposure in small intestinal villi was observed by immunohischemical staining. Also, western blot showed that PGS could effectively prevent endoplasmic reticulum (ER) stress-induced apoptosis caused by cisplatin in mice by restoring the activity of PERK (an ER kinase)-eIF2 α -ATF4 signal transduction pathway. Furthermore, molecular docking results of main saponins in PGS suggested a better binding ability with target proteins. In summary, the present work revealed the underlying protective mechanisms of PGS on intestinal injury induced by cisplatin in mice. [ABSTRACT FROM AUTHOR]

Successive evidence has established that maltol, a flavor‐enhancing agent, could provide resistance to oxidative stress‐induced tissue injury in various animal models though its benefits for aging‐induced liver and kidney injuries are still undetermined. In the present work, for demonstrating maltol's ameliorative effect and probable mechanism against aging‐induced liver and kidney injuries, D‐galactose (D‐Gal)‐induced animal in vivo and HEK293 cells in vitro models were established and results demonstrated that long‐term D‐Gal treatment increases the accumulation of advanced glycation end products (AGEs) in liver and kidney tissues, mitigates cell viability, and arrests the cycle. Interestingly, 4‐weeks maltol treatment at 50 and 100 mg/kg activated aging‐associated proteins including p53, p21, and p16 followed by inhibiting malondialdehyde (MDA)'s over‐production and increasing the levels of antioxidant enzymes. Therefore, decreases in cytochrome P450 E1 (CYP2E1) and 4‐hydroxydecene (4‐HNE)'s immunofluorescence expression levels are confirmed. Furthermore, maltol improved oxidative stress injury by activating the phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt) signaling pathway. In conclusion, the purpose of the present study was to estimate the mechanistic insights into maltol's role as an antioxidant in liver and kidney cell senescence and injury, which will reflect potential of therapeutic strategy for antiaging and aging‐related disease treatment. [ABSTRACT FROM AUTHOR]

Although the protective effect of ginsenoside on cisplatin-induced renal injury has been extensively studied, whether ginsenoside interferes with the antitumor effect of cisplatin has not been confirmed. In this paper, we verified the main molecular mechanism of 20(R)-ginsenoside Rg3 (R-Rg3) antagonizing cisplatin-induced acute kidney injury (AKI) through the combination of in vivo and in vitro models. It is worth mentioning that the two cell models of HK-2 and HepG2 were used simultaneously for the first time to explore the effect of the activation site of tumor-associated protein p53 on apoptosis and tumor suppression. The results showed that a single injection of cisplatin (20 mg/kg) led to weight loss, the kidney index of the mice increased, and creatinine (CRE) and blood urea nitrogen (BUN) levels in mice sharply increased. Continuous administration of R-Rg3 at doses of 10 and 20 mg/kg for 10 days could significantly alleviate this symptom. Similarly, R-Rg3 treatment reduced oxidative stress damage caused by cisplatin. Moreover, R-Rg3 could observably reduce the apoptosis and inflammatory infiltration of renal tubular cells induced by cisplatin. We used western blotting analysis to demonstrate that R-Rg3 restored cisplatin-induced AKI might be related to PI3K/AKT and NF- κ B mediated apoptosis and inflammation pathways. In the meantime, we also verified that R-Rg3 could activate different sites of p53 to control renal cell apoptosis induced by cisplatin without affecting its antitumor effect. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Platycodon grandiflorum Saponins (PGS) ameliorated scrotal heat-induced spermatogenic damage in mice. • Platycodon grandiflorum Saponins (PGS) inhibited heat stress (HS)-induced oxidative stress and apoptosis in mice. • Platycodon grandiflorum Saponins (PGS) partly regulated the MAPK signaling pathway in HS mice. Abstract The aim of the present study was designed to investigate that Platycodon grandiflorum saponins (PGS) exerted protective effects against testicular injury induced by scrotal hyperthermia. PGS (15, 30 mg/kg) were administered intragastrically to mice for 14 days, then exposed to a single scrotal heat treatment at 43 °C for 18 min on the 7th day. Heat stress (HS) induced spermatogenic damage was associated with a significant loss of leydig cells and the changes of serum testosterone, oxidative stress and apoptosis markers, and activated MAPK signaling pathway. In contrast, PGS treatment normalized HS-induced histopathological changes and prevented the activation of MAPK signaling pathway, which was contributed to oxidative stress and apoptosis in the testis of treated mice. In conclusion, our findings clearly demonstrated that PGS exhibited a significant protective effect against HS-induced testicular dysfunction, largely dependent upon the inhibition of oxidative stress associated apoptosis via partly regulation of MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Cisplatin is an effective anticancer chemotherapeutic agent, but the use of cisplatin in the clinic is severely limited by side effects. Nephrotoxicity is a major factor that contributes to the side effects of cisplatin chemotherapy. The aim of this research was to survey the nephroprotective effects of anthocyanin from the fruits of Panax ginseng (GFA) in a murine model of cisplatin-induced acute kidney injury. We observed that pretreatment with GFA attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels and histopathological injury induced by cisplatin. The formation of kidney malondialdehyde, heme oxygenase-1, cytochrome P450 E1 and 4-hydroxynonenal with a concomitant reduction in reduced glutathione was also inhibited by GFA, while the activities of kidney superoxide dismutase and catalase were all increased. GFA also inhibited the increase in serum tumour necrosis factor-α and interleukin-1β induced by cisplatin. In addition, the levels of induced nitric oxide synthase and cyclooxygenase-2 were suppressed by GFA. Furthermore, GFA supplementation inhibited the activation of apoptotic pathways by increasing B cell lymphoma 2 and decreasing Bcl2-associated X protein expression. In conclusion, the findings from the present investigation demonstrate that GFA pre-administration can significantly prevent cisplatin-induced nephrotoxicity, which may be related to its antioxidant, anti-apoptotic and antiinflammatory effects. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Although kidney injury caused by cisplatin has attracted much attention, cisplatin-induced cardiotoxicity is elusive. Our previous studies have confirmed that saponins (ginsenosides) from Panax quinquefolius can effectively reduce acute renal injuries. Our current study aimed to identify the potential effects of saponins from leaves of P. quinquefolius (PQS) on cisplatin-evoked cardiotoxicity. Methods: Mice were intragastrically with PQS at the doses of 125 and 250 mg/kg daily for 15 days. The mice in cisplatin group and PQS + cisplatin groups received four times intraperitoneal injections of cisplatin (3 mg/kg) two days at a time from the 7th day, respectively. All mice were killed at 48 h following final cisplatin injection. Body weights, blood and organic samples were collected immediately. Results: Our results showed that cisplatin-challenged mice experienced a remarkable cardiac damage with obvious histopathological changes and elevation of lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB) and cardiac troponin T (cTnT) concentrations and viabilities in serum. Cisplatin also impaired antioxidative defense system in heart tissues manifested by a remarkable reduction in reduced glutathione (GSH) content and superoxide dismutase (SOD) activity, demonstrating the overproduction of reactive oxygen species (ROS) and oxidative stress. Interestingly, PQS (125 and 250 mg/kg) can attenuate cisplatin-evoked changes in the above-mentioned parameters. Additionally, PQS administration significantly alleviated the oxidation resulted from inflammatory responses and apoptosis in cardiac tissues via inhibition of overexpressions of TNF-α, IL-1β, Bax, and Bad as well as the caspase family members like caspase-3, and 8, respectively. Conclusion: Findings from our present research clearly indicated that PQS exerted significant effects on cisplatin-induced cardiotoxicity in part by inhibition of the NF-κB activity and regulation of PI3K/Akt/apoptosis mediated signaling pathways. [ABSTRACT FROM AUTHOR]

Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, the in vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20( R )-Ginsenoside Rg3 (20( R )-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20( R )-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20( R )-Rg3 pretreatment. Moreover, 20( R )-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20( R )-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20( R )-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage. [ABSTRACT FROM AUTHOR]

The dried root of Platycodon grandiflorum (Jacq.) A.DC. (PG) is a traditional herb used in Asian countries and is widely used in formulas for the treatment of diabetes. Platycodin D (PD) is one of the most important components of PG. This study aimed to investigate the improvement effects and regulatory mechanisms of PD on kidney injury in a high-fat diet (HFD) combined with streptozotocin (STZ)-induced diabetic nephropathy (DN). Model mice were treated with oral gavage of the PD (2.5, 5 mg/kg) for 8 weeks. Determination of serum lipid and renal function-related indexes creatinine (CRE), and blood urea nitrogen (BUN) levels in mice, and histopathological section analysis of kidney. Molecular docking and molecular dynamics were utilized to study the binding ability of PD to target NF-κB and apoptosis signaling pathway-related proteins. Moreover, Western blot was used to test the expressions of NF-κB and apoptosis-related proteins. Vitro experiments were performed to validate the related mechanisms using RAW264.7 cells and HK2 cells cultured by high glucose. In vivo experiments, the administration of PD (2.5 and 5.0 mg/kg) reduced fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR) levels in DN mice, while lipid levels and renal function were significantly improved. Furthermore, PD significantly inhibited the development of DN in the model mice by regulating NF-κB and apoptotic signaling pathways, reduced the abnormal elevation of serum inflammatory factors TNF-α and IL-1β, and repaired renal cell apoptosis. In vitro experiments, NF-κB inhibitor ammonium pyrrolidine dithiocarbamate (PDTC) was used to confirm that PD can alleviate high glucose-induced inflammation in RAW264.7 cells and inhibit the release of inflammatory factors. And in HK2 cell experiments, it was verified that PD can inhibit ROS generation, reduce the loss of JC-1 and suppress HK2 cell injury by regulating NF-κB and apoptotic pathways. These data suggested that PD has the potential to prevent and treat DN and is a promising natural nephroprotective agent. [Display omitted] [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a major complication of diabetes. The kidney disease develops in nearly 20%–40% of type 2 diabetes (T2D) patients. Ginseng is the root of Panax ginseng C. A. Meyer and has been used in prevention and treatment of diseases for more than 2000 years as a traditional oriental medicine. The 20(R)-ginsenoside Rg3, an active saponin isolated from ginseng, can prevent and treat many diseases. The object of this research was to explore the alleviative effects of 20(R)-Rg3 on DN in mice. The T2D animal model was induced by continuous access to a high fat diet (HFD) combined with a single injection of 100 mg/kg streptozotocin (STZ) in C57BL/6 mice. The mice were treated by oral gavage of the 20(R)-Rg3 (10, 20 mg/kg) for 8 weeks. Functional and histopathological analyses of the kidneys were then performed. Protein expression levels of MAPKs and NF-κB signal pathways in the kidney were evaluated by western blotting. The expressions of HO-1 and NF-κB in the kidney were measured by fluorescent labeling staining. Other assessments including fasting blood glucose (FBG) levels, blood lipids, oxidative indicators, and inflammatory factors were all performed. Abnormally elevated FBG levels were observed in HFD/STZ mice, contributing significantly to the occurrence of DN. Simultaneously, HFD/STZ mice showed the rise of serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and the decrease in high density lipoprotein cholesterol (HDL-C). DN was evidenced by the overproduction of malondialdehyde (MDA), decreased levels of superoxide dismutase (SOD) and catalase (CAT) enzymatic activities, high levels of serum blood urea nitrogen (BUN) and creatinine (Cr). Simultaneously, the results of the immunofluorescence assay showed an increased expression level in NF-κB p65 while a decrease in antioxidant enzyme HO-1 was observed. Herein, 20(R)-Rg3 treatment for 8 weeks not only attenuated FBG levels and advanced glycation end products (AGEs) levels but also improved insulin (INS) level, blood lipids, oxidative stress, and renal function by regulating MAPKs and NF-κB signal pathways in DN mice. Taken together, the findings from the present study explicitly confirmed that 20(R)-Rg3 exerted ameliorative effects on DN mice via improving anti-oxidative activity and reducing renal inflammation. Image 1 [ABSTRACT FROM AUTHOR]