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Ginsenoside Rd attenuated hyperglycemia via Akt pathway and modulated gut microbiota in streptozotocin-induced diabetic rats.

ABSTRACT: Ginsenoside Rd is a protopanaxadiol abundant in Panax ginseng and Panax notoginseng. It has been reported that ginsenoside Rd possesses various health benefits, such as anti-diabetic, anti-tumor and anti-inflammatory. This work explored the effects of ginsenoside Rd on hyperglycemia and gut microbiota in streptozotocin-induced diabetic rats. Results showed that 5-week ginsenoside Rd (20 mg/kg) treatment significantly improved hyperglycemia in diabetic rats. Besides, ginsenoside Rd promoted glycogen synthesis via activating Akt pathway. It also inhibited hepatic gluconeogenesis, which was associated with inhibiting phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. We further found that ginsenoside Rd treatment increased the diversity of gut microbiota, increased the abundance of beneficial bacteria, such as SMB53, rc4-4 and Ruminococcus, and reduced the abundance of conditional pathogenic bacteria. These results indicated that ginsenoside Rd has the potential for diabetic intervention.

SUBMITTER: Wang W

PROVIDER: S-EPMC10074500 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Ginsenoside Rd attenuated hyperglycemia via Akt pathway and modulated gut microbiota in streptozotocin-induced diabetic rats.

Wang Wei W Guan Fengtao F Sagratini Gianni G Yan Jie J Xie Jiahan J Jin Zhibo Z Liu Meihong M Liu Huimin H Liu Jingsheng J

Current research in food science 20230321

Ginsenoside Rd is a protopanaxadiol abundant in Panax ginseng and Panax notoginseng. It has been reported that ginsenoside Rd possesses various health benefits, such as anti-diabetic, anti-tumor and anti-inflammatory. This work explored the effects of ginsenoside Rd on hyperglycemia and gut microbiota in streptozotocin-induced diabetic rats. Results showed that 5-week ginsenoside Rd (20 mg/kg) treatment significantly improved hyperglycemia in diabetic rats. Besides, ginsenoside Rd promoted glyco ...[more]

PMID: 37033737

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Project description:Introduction: Chemicals, such as MNU (N-methyl-N-nitrosourea) and NaIO3 (sodium iodate), are widely used to induce retinal degeneration in rodents. Streptozotocin (STZ) is an analog of N-acetyl glucosamine in which an MNU moiety is linked to a hexose and has a special toxic effect on insulin-producing pancreatic β-cells. It is commonly used to induce hyperglycemia to model diabetes. While intracerebroventricular injection of STZ can produce Alzheimer's disease independent of hyperglycemia, most retinal studies using STZ focus on the effects of hyperglycemia on the retina, but whether STZ has any impact on retinal cells independent of hyperglycemia is unknown. We aimed to investigate the role of cytotoxicity of STZ in rat retina. Methods: Intravitreal or subcutaneous injection of STZ was performed on newborn rats. Electroretinogram (ERG) and H&E staining investigated retinal function and morphological changes. Retinal cell types, cell death, proliferation, inflammation, and angiogenesis were studied by immunostaining. RNA sequencing was performed to examine the transcriptome changes of retinal cells after intravitreal injection of STZ. Results: Intravitreal (5 μg or 10 μg) or subcutaneous (30 mg/kg) injection of STZ at the early stage of newborn rats couldn't induce hyperglycemia but caused NSIR (Neonatal STZ-induced retinopathy), including reduced ERG amplitudes, retinal rosettes and apoptosis, cell cycle arrest, microglial activation, and delayed retinal angiogenesis. STZ did not affect the early-born retinal cell types but significantly reduced the late-born ones. Short-term and long-term hyperglycemia had no significant effects on the NSIR phenotypes. RNA sequencing revealed that STZ induces oxidative stress and activates the p53 pathway of retinal cells. Locally or systemically, STZ injection after P8 couldn't induce SINR when all retinal progenitors exit the cell cycle. Conclusion: NSIR in rats is independent of hyperglycemia but due to STZ's direct cytotoxic effects on retinal progenitor cells. NSIR is a typical reaction to STZ-induced retinal oxidative stress and DNA damage. This significant finding suggests that NSIR may be a valuable model for studying retinal progenitor DNA damage-related diseases, potentially leading to new insights and treatments.

Project description:IntroductionDiphenyl diselenide (DPDS) ameliorates nephropathy in streptozotocin (STZ)-induced type 1 diabetic rats by inhibiting oxidative stress and inflammatory reactions. However, it has not been clarified whether DPDS alleviates type 1 diabetic kidney disease (DKD) is related to the inhibition of extracellular matrix (ECM) production and the regulation of intestinal flora disorder.MethodsThe present study investigated the effects of DPDS on ECM generation in the kidney and intestinal microflora composition in feces. The rats were orally administered DPDS or metformin for eight weeks. Various indices were measured to assess the severity of renal injury. After euthanizing the rats, oxidative stress markers in serum and kidney were assessed using biochemical methods, and the expressions of ECM-related proteins in kidney were analyzed using Western blot. Additionally, 16S rRNA high-throughput sequencing was used to evaluate the diversity and composition of the intestinal flora in feces.ResultsThe results showed DPDS and metformin improved the DKD in STZ rats, as evidenced by decreased blood glucose, BUN, urine volume, urine microalbumin, urinary β2 microglobulin, and improvement of renal pathological morphology. Furthermore, DPDS intervention markedly reduced the protein expression of α-SMA, COI Ⅳ, FN, and vimentin in the kidneys. Besides, DPDS not only improved dyslipidemia in STZ diabetic rats, but also enhanced the activities of antioxidant enzymes, decreased the level of MDA in serum and kidney, and regulated the expression of proteins related to the Nrf2/Keap1 signaling pathway in the kidney. Moreover, we found that DPDS could selectively improve the relative abundance of probiotics as well as the diversity of flora, thus ameliorating the intestinal microbial composition of the STZ rats, significantly regulating the intestinal microbial homeostasis.DiscussionOverall, DPDS inhibited ECM production and improved renal pathological changes, which may be related to reducing oxidative stress damage in the kidney and improving intestinal flora imbalance, providing data support for the further development and application of DPDS in DKD.

Project description:The effect of livingstone potato (Plectranthus esculenthus N.E.Br) on serum glucose, glycated hemoglobin (HbA1C), serum triglyceride, total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), hepatic malic enzyme (ME), isocitrate dehydrogenase (IDH) and catalase activities of Streptozotocin induced diabetic rats were investigated using standard techniques. The atherogenic index (AI) and coronary risk index (CRI) of the rats were calculated as the ratios of LDL to HDL and total cholesterol to HDL, respectively. The serum glucose of the non-diabetic, diabetic control and diabetic rats given livingstone potato incorporated feeds (test feed) were 92.58 ± 3.97, 352.30 ± 4.88 and 165.50 ± 7.88 mg/dl, respectively. Intake of the test feed by the diabetic rats of group 3, resulted in significant (P < 0.05) decrease of their serum glucose, HbA1c, triglyceride, cholesterol, LDL, VLDL, AI and CRI but significant increase (P < 0.05) of hepatic levels of ME, IDH, catalase and serum HDL compared with the diabetic control rats that had significant alteration of these parameters (P < 0.05) compared with the non-diabetic rats. The feed intakes of the non-diabetic, diabetic control and diabetic rats given the test feed were 133.34 ± 1.32, 137.84 ± 5.77 and 146.38 ± 4.33 g/rat/week by the last week of experimentation. The diabetic control rats recorded significant loss of weight (P < 0.05) compared with the non diabetic rats despite increased feed intake. Chemical analysis of the standard and test feeds showed that the standard rat feed contained 15.00 ± 0.78% protein, 7.24 ± 1.20% fat, 31.55 ± 2.62% carbohydrates, energy value of 290.65 ± 4.77 kcal/100 g, 10% crude fiber and 0.12 ± 0.04 mg Gallic Acid Equivalent while the test feed contained 40.10 ± 0.16% carbohydrates, 17.22 ± 0.40% protein, 22.16 ± 0.34% fat, energy value of 428.70 ± 2.12 kcal/100 g, 8.51 ± 0.16% crude fiber, 1.3 ± 0.2 mg Gallic Acid Equivalent/g of sample and strong antioxidant activity comparable to standard quercetin. The study shows the potentials of livingstone potato in the management of diabetes and hyperlipidemia.

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Ginsenoside Rd attenuated hyperglycemia via Akt pathway and modulated gut microbiota in streptozotocin-induced diabetic rats.

Publications

Ginsenoside Rd attenuated hyperglycemia via Akt pathway and modulated gut microbiota in streptozotocin-induced diabetic rats.

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