Effect of β-sitosterol on glucose homeostasis by sensitization of insulin resistance via enhanced protein expression of PPRγ and glucose transporter 4 in high fat diet and streptozotocin-induced diabetic rats

Sundaram, R.; Meenatchi, Packirisamy; Muthu, K.; Vasu, Ganesh; Gopalakrishnan, Ramamurthy; Gothandam, Kirubananthan; Thiruppathi, Muthusamy

doi:10.1007/s10616-020-00382-y

Cited by 35 publications

(28 citation statements)

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“…For example, Gumede et al discovered that β-sitosterol prevents high-fructose diet-induced metabolic dysfunction in female rats, including visceral obesity, hypertriglyceridemia, and hypoadiponectinemia [68]. Another in vivo study showed that the administration of β-sitosterol significantly increased the levels of insulin, hemoglobin, and the PPAR-c and GLUT4 proteins, alleviated insulin resistance, and decreased the plasma glucose levels in high-fat diet-and streptozotocin-induced diabetic rats [69]. In addition, a clinical cohort study revealed rather specific negative correlations between the serum sitosterol level and the serum IL6 and TNF-α levels in both subjects with and without diabetes, suggesting the anti-inflammatory potential of β-sitosterol [70].…”

Section: Discussionmentioning

confidence: 99%

Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia

Gao

Shi

Jia

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as β-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.

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Section: Discussionmentioning

confidence: 99%

Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia

Gao

Shi

Jia

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Quercetin is an important flavonoid that has been normally viewed as a great antioxidant and anti-inflammatory molecule [ 35 – 37 ] and can prevent endothelial dysfunction and myocardial ischemia [ 38 ]. Beta-sitosterol exerted protective actions against myocardial injury [ 39 ] and is used in the treatment of hypercholesterolemia [ 40 ]. Kaempferol has antioxidant, anti-inflammatory effect [ 41 ] and protects against cardiac hypertrophy [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Research on Effect and Mechanism of Xuefu Zhuyu Decoction on CHD Based on Meta-Analysis and Network Pharmacology

Kui

Gao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Xuefu Zhuyu Decoction (XFZY) is an ancient compound widely used in the treatment of coronary heart disease. However, its efficacy evaluation is not complete and its mechanism of action is not clear enough. In an attempt to address these problems, the efficacy was evaluated by meta-analysis and the mechanism was elucidated by the network pharmacology method. We systematically searched relevant studies in PubMed, Chinese National Knowledge Infrastructure Database (CNKI), Cochrane Library, Wanfang Data, and other databases from 2007 to 2019. The association between XFZY treatment and CHD was estimated by risk ratio (RR) and corresponding 95% confidence intervals (95% CIs). The compounds and the potential protein targets of XFZY were obtained from TCMSP, and active compounds were selected according to their oral bioavailability and drug similarity. The potential genes of coronary heart disease were obtained from TTD, OMIM, and GeneCards. The potential pathways related to genes were determined by GO and KEGG pathway enrichment analyses. The compound-target and compound-target-pathway networks were constructed. Molecular docking validates the component and the target. A total of 21 studies including 1844 patients were enrolled in the present meta-analysis, indicating that XFZY has a greater beneficial on total effect (fixed effect RR = 1.30; 95% Cl: 1.24–1.36; P = 0.82 ; I2 = 0.0%) and electrocardiogram efficacy (fixed effect RR = 1.40; 95% Cl: 1.26–1.56; P = 0.96 ; I2 = 0.0%) compared with the control group. A total of 1342 components in XFZY were obtained, among which, 241 were chosen as bioactive components. GO and KEGG analyses got top 10 significantly enriched terms and 10 enriched pathways. The C-T network included 192 compounds and 3085 targets, whereas the C-T-P network included 10 compounds, 109 targets, and 5 pathways. There was a good binding activity between the components and the targets. XFZY has the curative effect on coronary heart disease, and its mechanism is related to 10 compounds, 10 core targets, and 5 pathways.

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“…ere are 3 common components: and Chuanxiong Rhizoma by comparing specific herbs of the four strategies. Analogous to cholesterol structure, beta-sitosterol as a plant-derived compound is generally utilized to treat hypercholesterolemia and coronary artery disease [34]. Besides beta-sitosterol, stigmasterol belongs to phytosterol that is in favor of reducing heart attack risk via lowering cholesterol levels in a natural way [35].…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis on Single- and Multiherb Strategies in Coronary Artery Atherosclerosis Therapy

Cao

Liu

Zhang

et al. 2021

Cardiology Research and Practice

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Herbal medicine unswervingly serves human health by modernizing preparation and administration. Coronary artery atherosclerosis is a serious threat to human health and survival all over the world. Following experimental and clinical evidence, we collected four herbal treatments containing herbal strategy I (San Qi), II (Injectio Salvia Miltiorrhizae), III (Danhong injection), and IV (Taoren Honghua Jian granule) against coronary artery disease. In order to analyze their similarities and differences in controlling coronary artery atherosclerosis, we investigated each herb of four strategies and revealed that the number of active components and molecule targets is increasing with the herb category of herbal strategy. Nitric oxide-associated carbonate dehydratase activity and nitrogen metabolism are tacitly enriched by target corresponding genes with statistical significance in four strategies. The herbal strategy with multiherb not merely possesses more amounts and interactions of target proteins than the strategy with single-herb but also enlarges interaction partners of target proteins like PTPN11 and STAT3 in strategy II, III, and IV. Whereas single-herb also involves regulating network core proteins in consistent with compatibility, such as SRC and PIK3R1 that are mostly targeted by strategy I, III, and IV. Comparing the targets of the herbal strategies and three existing drugs (atenolol, pravastatin and propranolol) and the symbols of coronary artery atherosclerosis, we discovered that MAOA, HTR1A, and ABCG2 are overlapping in the three groups. Hence, our work enables people to better understand the connections and distinctions of single- and multiherb on the healing of coronary artery atherosclerosis.

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Effect of β-sitosterol on glucose homeostasis by sensitization of insulin resistance via enhanced protein expression of PPRγ and glucose transporter 4 in high fat diet and streptozotocin-induced diabetic rats

Cited by 35 publications

References 28 publications

Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia

Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia

Research on Effect and Mechanism of Xuefu Zhuyu Decoction on CHD Based on Meta-Analysis and Network Pharmacology

Comparative Analysis on Single- and Multiherb Strategies in Coronary Artery Atherosclerosis Therapy

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