INTERNATIONAL IMMUNOPHARMACOLOGY
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2021
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IF 4.932
Xiaoqi Sun,Xiaotian Wang,Qianqian He,Muqing Zhang,Li Chu,Yang Zhao,Yongchao Wu,Jianping Zhang,Xue Han,Xi Chu,Zhonglin Wu,Shengjiang Guan
Baicalin (BA), a kind of flavonoids compound, comes from Scutellaria baicalensis Georgi (a kind of perennial herb) and has beneficial effects on the cardiovascular system through anti-oxidant, anti-inflammation, and anti-apoptosis actions. However, the therapeutic effects and latent mechanisms of BA on arsenic trioxide (ATO)-induced cardiac toxicity has not been reported. The present research was performed to explore the effects and mechanisms of BA on ATO-induced heart toxicity. Male Kunming mice were treated with ATO (7.5 mg/kg) to induce cardiac toxicity. After the mice received ATO, BA (50 and 100 mg/kg) was administered for estimating its cardioprotective effects. Statistical data demonstrated that BA treatment alleviated electrocardiogram abnormalities and pathological injury caused by ATO. BA could also lead to recovery of CK and LDH activities to normal range and cause a decrease in MDA levels and ROS generation, augmentation of SOD, CAT, and GSH activities. We also found that BA caused a reduction in the expression of proinflammatory cytokines, such as TNF-α and IL-6. Moreover, BA attenuated ATO-induced apoptosis by promoting the expression of Bcl-2 and suppressing the expression of Bax and caspase-3. TUNEL test result demonstrated BA caused impediment of ATO-induced apoptosis. Furthermore, BA treatment suppressed the high expression of TLR4 , NF-κB and P-NF-κB caused by ATO. In conclusion, these results indicate that BA may alleviate ATO-induced cardiac toxicity by restraining oxidative stress, apoptosis, and inflammation, and its mechanism would be associated with the inhibition of the TLR4/NF-κB signaling pathway.
研究领域:
药理学
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毒理学
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心脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yujun Xie,Luyao An,Xiaoyan Wang,Yajie Ma,Alamusi Bayoude,Xinxin Fan,Boyang Yu,Renshi Li
Ethnopharmacological relevance Dioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. Aim of the study This study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. Materials and methods The active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. Results CYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p -NF- κ B and p -I κ B- α expression levels and inhibiting the generation of IL-6, TNF- α , and IL-1 β . At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. Conclusion This study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.
研究领域:
药理学
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植物化学
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胃肠病学
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分子生物学
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炎症研究
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氧化应激
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Jirui Lang,Li Li,Yunyun Quan,Ruirong Tan,Jinbiao Zhao,Min Li,Jin Zeng,Shilong Chen,Ting Wang,Yong Li,Junning Zhao,Zhujun Yin
Wuwei Shexiang Pill (WSP) is a Tibetan traditional medicine, which has been demonstrated to exhibit potent anti-inflammatory and anti-gout effects. However, the specific pharmacological mechanism is not elucidated clearly. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied to investigate the alteration of serum metabolites induced by WSP treatment in MSU-induced gouty rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-gout effect of WSP. The pharmacodynamic data discovered that WSP could ameliorate ankle swelling and inflammatory cell infiltration, as well as downregulate the protein expression of IL-1β, p-NF-κB p65, and NLRP3 in the synovial membrane and surrounding tissues of gouty ankles. LC-MS-based metabolomics revealed that there were 30 differential metabolites in the serum between sham-operated rats and gouty ones, which were mainly involved in the metabolism of fructose and mannose, primary bile acid biosynthesis, and cholesterol metabolism. However, compared to the model group, WSP treatment upregulated 11 metabolic biomarkers and downregulated 31 biomarkers in the serum. KEGG enrichment analysis found that 27 metabolic pathways contributed to the therapeutic action of WSP, including linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. The comprehensive analysis-combined network pharmacology and metabolomics further revealed that the regulatory network of WSP against gout might be attributed to 11 metabolites, 7 metabolic pathways, 39 targets, and 49 active ingredients of WSP. In conclusion, WSP could ameliorate the inflammation of the ankle in MSU-induced gouty rats, and its anti-gout mechanism might be relevant to the modulation of multiple metabolic pathways, such as linoleic acid metabolism, phenylalanine metabolism, and pantothenate and CoA biosynthesis. This study provided data support for the secondary development of Chinese traditional patent medicine.
研究领域:
药理学
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代谢组学
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传统中药
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炎症生物学
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生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2017
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IF 3.154
Jiarui Nie,Yaning Chang,Yujia Li,Yingjun Zhou,Jiawen Qin,Zhen Sun,Haibin Li
Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.
研究领域:
药理学
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内分泌学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·Vol. 29
·期 4
·1000-1011
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IF 5.5
Di Zhang,Bei Jing,Zhen-ni Chen,Xin Li,Hui-mei Shi,Ya-chun Zheng,Shi-quan Chang,Li Gao,Guo-ping Zhao
Introduction Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. Methods Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. Results RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. Conclusion Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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