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      The Medicinal Plant Pair Bupleurum chinense- Scutellaria baicalensis – Metabolomics and Metallomics Analysis in a Model for Alcoholic Liver Injury

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          Abstract

          Traditional Chinese Medicine (TCM), a complex natural herbal medicine system, has increasingly attracted attention from all over the world. Most research has illustrated the mechanism of TCM based on the active components or single herbs. It was fruitful and effective but far from satisfactory as it failed to gain insights into the interactivity and combined effects of TCM. In this work, we used Bupleurum chinense ( B. chinense DC, a species in the genus Bupleurum, family Apiaceae) and Scutellaria baicalensis ( S. baicalensis Georgi, a species in the genus Scutellaria, family Lamiaceae), an herbal pair in TCM, to illustrate the combined effect. We compared the diverse effects between the B. chinense-S. baicalensis herbal pair and its compositions in an animal model of Alcoholic Liver Injury to highlight the advantages of the formula. Biochemical and histological indicators revealed that the effect of B. chinense-S. baicalensis was better than its individual parts. Furthermore, metabolite profiling of the serum, liver tissue, and feces were conducted to reveal that the herbal pair largely presented its effects through enhanced tissue penetration to maintain liver-located intervention with less global and symbiotic disturbance. Furthermore, we analyzed the distribution of the metal elements in extracts of the serum and liver tissue and found that the herbal pair significantly regulated the distribution of endogenous selenium in liver tissue. As selenium plays an important role in the anti-oxidative and hepatoprotective effects, it may be the reason for combined effects in BS formula. This research could open new perspectives for exploring the material basis of combined effects in natural herbal medicine.

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          Most cited references47

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          The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin.

          Five extracts (n-hexane, chloroform, ethyl acetate, n-butanol and water) of Scutellaria rivularis Benth. were evaluated for their anti-inflammatory activity against carrageenan-induced paw edema in rats and compared with indomethacin. The result indicated that chloroform extract proved to be the most effective in all of the extracts. Consequently, three major components (baicalin, baicalein and wogonin) of the chloroform extract were further tested for their anti-inflammatory activity using the same model. It was found that baicalin exhibits the greatest inhibition activity against carrageenan-induced rat paw edema.
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            Saikosaponin a and its epimer saikosaponin d exhibit anti-inflammatory activity by suppressing activation of NF-κB signaling pathway.

            Saikosaponin a (SSa) and its epimer saikosaponin d (SSd) are major triterpenoid saponin derivatives from Radix bupleuri (RB), which has been long used in Chinese traditional medicine for treatment of various inflammation-related diseases. In the present study, the anti-inflammatory activity, as well as the underlying mechanism, of SSa and SSd was investigated in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that both SSa and SSd significantly inhibited the expression of inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW264.7 cells, and finally resulted in the reduction of nitric oxide (NO) and prostaglandin E(2) (PGE(2)). In addition, LPS-induced production of major pro-inflammatory cytokines: the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), was suppressed in a dose-dependent manner by the treatment of SSa or SSd in RAW264.7 cells. Further analysis revealed that both SSa and SSd could inhibit translocation of nuclear factor-κB (NF-κB) from the cytoplasm to the nucleus in the LPS-induced RAW264.7 cells. Furthermore, SSa and SSd exhibited significant anti-inflammatory activity in two different murine models of acute inflammation, carrageenan-induced paw edema in rats and acetic acid-induced vascular permeability in mice. In conclusion, SSa and SSd showed potent anti-inflammatory activity through inhibitory effects on NF-κB activation and thereby on iNOS, COX-2 and pro-inflammatory cytokines. Copyright © 2012 Elsevier B.V. All rights reserved.
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              Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet

              Aim: Baicalin, one of the major flavonoids in Scutellaria baicalensis, possesses antioxidant and anti-inflammatory properties. However, the effects of baicalin on metabolic disorders and hepatic steatosis have not been investigated. Methods: Body weight was examined in high-fat diet (HFD)-fed rats with or without baicalin treatment. At the end of the experiment, serum biochemical parameters, liver histology and lipid profile were analyzed to assess whether the animals were suffering from metabolic disorders or hepatic steatosis. In the liver, the phosphorylation of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and the gene expression of some enzymes involved in lipogenesis were examined. The effects of baicalin on the phosphorylation of AMPK and lipid accumulation induced by high glucose in human hepatoma HepG2 cells were also examined. Results: Baicalin (80 mg/kg) administered ip for 16 weeks suppressed body weight gain in HFD-fed rats. Weight reduction was accompanied by the reduction of visceral fat mass. Baicalin significantly decreased the elevated serum cholesterol, free fatty acid and insulin concentrations caused by the HFD. Baicalin also suppressed systemic inflammation by reducing the serum level of tumor necrosis factor α. Baicalin reduced hepatic lipid accumulation, enhanced the phosphorylation of AMPK and ACC and down-regulated genes involved in lipogenesis, including fatty acid synthase and its upstream regulator SREBP-1c. In HepG2 cells, baicalin (5 and 10 μmol/L) increased the phosphorylation of AMPK and decreased lipid accumulation following the addition of high glucose. Conclusion: Our study suggests that baicalin might have beneficial effects on the development of hepatic steatosis and obesity-related disorders by targeting the hepatic AMPK.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                20 March 2019
                2019
                : 10
                : 254
                Affiliations
                [1] 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine , Shanghai, China
                [2] 2Institute for Interdisciplinary Medicine Sciences, Shanghai University of Traditional Chinese Medicine , Shanghai, China
                [3] 3Frontier Medical Service Brigade, Army Medical University , Hutubi, China
                [4] 4School of Traditional Dai-Thai Medicine, West Yunnan University of Applied Sciences , Jinghong, China
                [5] 5School of Pharmacy, Lanzhou University , Lanzhou, China
                Author notes

                Edited by: Xijun Wang, Heilongjiang University of Chinese Medicine, China

                Reviewed by: Rufeng Wang, Beijing University of Chinese Medicine, China; Haolong Liu, Peking University Health Science Center, China

                *Correspondence: Yongyu Zhang, dryyz@ 123456sina.com Jianye Dai, daijy@ 123456lzu.edu.cn Ningning Zheng, zhengningning02@ 123456163.com

                These authors have contributed equally to this work

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Article
                10.3389/fphar.2019.00254
                6445227
                8ddc37d3-8ccf-4d16-af90-841b4767253e
                Copyright © 2019 Dang, Li, Sun, Wang, Lin, Zhang, Dai and Zheng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 August 2018
                : 28 February 2019
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 51, Pages: 10, Words: 0
                Categories
                Pharmacology
                Original Research

                Pharmacology & Pharmaceutical medicine
                metabolomics,metallomics,bupleurum chinense-scutellaria baicalensis,herbal pair,alcoholic liver injury

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